| 1. |
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| 2. |
- Aaby, Peter, et al.
(författare)
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Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:29-30, s. 5718-5718
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Live vaccines including BCG and measles may have non-targeted beneficial effects on childhood survival in areas with high mortality. The authors therefore undertook a survey of vaccinia scars to evaluate subsequent mortality. SUBJECTS: Based on a population census, a cohort of 1893 adults in urban Guinea-Bissau was examined in 1998 and followed until 2002. MAIN OUTCOME MEASURE: All cause mortality, excluding accidents. RESULTS: The median age of vaccinia vaccinations had been 16-18 years. Adults with a vaccinia scar had a mortality ratio (MR) of 0.60 (0.41-0.87) compared to those without any scar. The effect was stronger for women. Mortality decreased with each additional vaccinia scar (MR=0.73 (0.56-0.95)). Among 502 individuals with information on HIV infection, the age-adjusted HIV-2 prevalence was 2.45 (1.06-5.65) for those with a vaccinia scar. Control for district, ethnic group, schooling, place of birth, quality of housing and HIV status had little effect on the estimate. Since vaccinia and BCG scars could have been confused, mortality for adults with vaccinia and/or BCG scar was compared to those without, the MR being 0.61 (0.41-0.89). CONCLUSION: Known cultural or socio-economic factors possibly associated with access to vaccination had no influence on the mortality ratio for having a vaccinia scar. Hence, vaccinia vaccination may have a prolonged beneficial effect on adult survival.
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| 3. |
- Abu-Elyazeed, R R, et al.
(författare)
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Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age : results from a randomised, controlled, double-blind trial
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:51, s. 6136-6143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.
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| 4. |
- Ahmed, S., et al.
(författare)
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The economic burden of rotavirus hospitalization among children < 5 years of age in selected hospitals in Bangladesh
- 2021
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 39:48, s. 7082-7090
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rotavirus is a common cause of severe acute gastroenteritis among young children. Estimation of the economic burden would provide informed decision about investment on prevention strategies (e.g., vaccine and/or behavior change), which has been a potential policy discussion in Bangladesh for several years. Methods: We estimated the societal costs of children <5 years for hospitalization from rotavirus gastroenteritis (RVGE) and incidences of catastrophic health expenditure. A total of 360 children with stool specimens positive for rotavirus were included in this study from 6 tertiary hospitals (3 public and 3 private). We interviewed the caregiver of the patient and hospital staff to collect cost from patient and health facility perspectives. We estimated the economic cost considering 2015 as the reference year. Results: The total societal per-patient costs to treat RVGE in the public hospital were 126 USD (95% CI: 116-136) and total household costs were 161 USD (95% CI: 145-177) in private facilities. Direct costs constituted 38.1% of total household costs. The out-of-pocket payments for RVGE hospitalization was 23% of monthly income and 76% of households faced catastrophic healthcare expenditures due to this expense. The estimated total annual household treatment cost for the country was 10 million USD. Conclusions: A substantial economic burden of RVGE in Bangladesh was observed in this study. Any prevention of RVGE through cost-effective vaccination or/and behavioural change would contribute to substantial economic benefits to Bangladesh. (c) 2021 Elsevier Ltd. All rights reserved.
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| 5. |
- Ahmed, Tanvir, 1970, et al.
(författare)
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CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28:2, s. 422-9
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Tidskriftsartikel (refereegranskat)abstract
- Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral((R)) containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10-18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P<0.01) and IFN-gamma production (P<0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P>0.05). The IFN-gamma production was significantly higher (P<0.01) but the blast formation comparable (P>0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P<0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-gamma as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.
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| 6. |
- Akhtar, Zubair, et al.
(författare)
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Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial
- 2023
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 41:48, s. 7159-7165
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Tidskriftsartikel (refereegranskat)abstract
- Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.
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| 7. |
- Andersen, Andreas, et al.
(författare)
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The immunological effect of revaccination with Bacille Calmette-Guerin vaccine at 19 months of age
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 31:17, s. 2137-2144
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bacille Calmette-Guerin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination. Methods: Children were randomized to BCG or nothing. Blood was sampled 6-11 weeks after randomization (early sample group) or 5-9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-gamma, interleukin (IL)-13, tumor-necrosis-factor (TNF)-alpha, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied. Results: Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-gamma (geometric mean ratio (GMR) = 4.54 (95% confidence interval: 3.13-6.58)) and IL-13 (GMR = 1.43 (1.00-2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR = 1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-alpha/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p = 0.03). In children without MN, BCG was associated with reduced TNF-alpha response in the early sample group (p = 0.006), and increased IL-10 in the late sample group (p = 0.03). Conclusion: BCG revaccination resulted in a strong IFN-gamma response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-alpha and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination. (C) 2013 Elsevier Ltd. All rights reserved.
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| 8. |
- Andersson, Charlotta Rydgard, et al.
(författare)
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Vaccine failures after active immunisation against tick-borne encephalitis
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:16, s. 2827-2831
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a major disease of the central nervous system in Europe and is endemic in Sweden with about 200 notified cases annually. The far most effective protective measure against TBE is active immunisation. The vaccines available today induce a high degree of protection in field studies. However, vaccine failures have occasionally been reported and may be overlooked due to different, and sometimes confusing, antibody kinetics in vaccinees with TBEV infection. In this study, 27 patients with clinical and serological evidences of TBE despite adequate immunisation are presented. Vaccination failure is characterized by a slow, and initially non-detectable, development of the specific TBEV-IgM response, seen together with a rapid rise of IgG and neutralising antibodies in serum. The majority (70%) of the patients were more than 50 years of age, which may implicate a need for a modified immunisation strategy in the elderly.
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| 9. |
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| 10. |
- Arama, Charles, et al.
(författare)
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A recombinant Bacille Calmette-Guerin construct expressing the Plasmodium falciparum circumsporozoite protein enhances dendritic cell activation and primes for circumsporozoite-specific memory cells in BALB/c mice
- 2012
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 30:37, s. 5578-5584
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Tidskriftsartikel (refereegranskat)abstract
- A protective malaria vaccine may induce both high levels of neutralising antibodies and strong T-cell responses. The Plasmodium falciparum circumsporozoite protein (CSp) is a leading pre-erythrocytic vaccine candidate. CSp is a week immunogen per se, but Mycobacterium bovis Bacille Calmette-Guérin (BCG) has excellent adjuvant activity and has been utilized as a vector to deliver heterologous vaccine candidate antigens. It is safe in immunocompetent individuals and inexpensive to produce. We assessed in vitro and in vivo a recombinant BCG-expressing CSp (BCG-CS) as malaria vaccine candidate. Immunisation of BALB/c mice with BCG-CS augmented numbers of dendritic cells (DCs) in draining lymph nodes and in the spleen. The activation markers MHC-class-II, CD40, CD80 and CD86 on DCs were significantly upregulated by BCG-CS as compared to wild-type BCG (wt-BCG). In vitro stimulation of bone marrow-derived DCs and macrophages with BCG-CS induced IL-12 and TNF-α production. BCG-CS induced higher phagocytic activity in macrophages as compared to wt-BCG. Immunogenicity studies show that BCG-CS induced CS-specific antibodies and IFN-γ-producing memory cells. In conclusion, BCG-CS is highly efficient in activating antigen-presenting cells (APCs) for priming of adaptive immunity. Implications for the rational design of novel vaccines against malaria and TB, the two major devastating poverty-related diseases, are discussed.
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| 11. |
- Arama, Charles, et al.
(författare)
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Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guerin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice
- 2012
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 30:27, s. 4040-4045
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines. Results: In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-gamma and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses. Conclusion: The increased IFN-gamma-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.
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| 12. |
- Arbyn, Marc, et al.
(författare)
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Clinical applications of HPV testing: A summary of meta-analyses
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:Suppl. 3, s. 78-89
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. Material and methods: A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Results: Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recur-rent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%) loss in specificity, in comparison with isolated HC2 screening. Conclusions: Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway. (c) 2006 Elsevier Ltd. All rights reserved.
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| 13. |
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| 14. |
- Areschoug, Thomas, et al.
(författare)
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Host-pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development.
- 2004
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 22 Suppl 1:Suppl 1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes (group A streptococcus) causes a variety of diseases, including acute pharyngitis, impetigo, rheumatic fever and the streptococcal toxic shock syndrome. Moreover, S. pyogenes was responsible for the classical example of a nosocomial infection, the epidemics of puerperal fever (childbed fever) that caused the death of numerous women in earlier centuries. The most extensively studied virulence factor of S. pyogenes is the surface M protein, which inhibits phagocytosis and shows antigenic variation. Recent data indicate that many M proteins confer phagocytosis resistance because the variable N-terminal region has non-overlapping sites that specifically bind two components of the human immune system, the complement inhibitor C4b-binding protein (C4BP) and IgA-Fc. Concerning puerperal fever, molecular and epidemiological analysis suggests that the S. pyogenes surface protein R28 may have played a pathogenetic role in these epidemics. This article summarizes the properties of M protein and the R28 protein and considers a potential problem encountered in connection with the use of animal models for vaccine development.
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| 15. |
- Arko-Mensah, John, et al.
(författare)
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Resistance to mycobacterial infection : a pattern of early immune responses leads to a better control of pulmonary infection in C57BL/6 compared with BALB/c mice.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 27:52, s. 7418-27
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we have compared the immunological responses associated with early pulmonary mycobacterial infection in two mouse strains, BALB/c and C57BL/6 known to exhibit distinct differences in susceptibility to infection with several pathogens. We infected mice via the intranasal route. We have demonstrated that BALB/c was less able to control mycobacterial growth in the lungs during the early phase of pulmonary infection. Our results showed that during the early phase (day 3 to week 1), BALB/c mice exhibited a delay in the production of TNF and IFN-gamma in the lungs compared to C57BL/6 mice. Levels of IL-12 and soluble TNF receptors (sTNFR) were comparable between the mouse strains. The cellular subset distribution in these mice before and after infection showed a higher increase in CD11b+ cells in the lungs of C57BL/6, compared to BALB/c as early as day 3 postinfection. At early time points, higher levels of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein 1 (MIP)-alpha were detected in C57BL/6 than BALB/c mice. In vitro, BCG-infected bone marrow derived macrophages (BMM) from both mouse strains displayed similar capacities to either phagocytose bacteria or produce soluble mediators such as TNF, IL-12 and nitric oxide (NO). Although IFN-gamma stimulation of infected BMM in both mouse strains resulted in the induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The above observations indicate that the chain of early, possibly innate immunological events occurring during pulmonary mycobacterial infection may directly impact on increased susceptibility or resistance to infection.
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| 16. |
- Askling, H. H., et al.
(författare)
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Immunogenicity of delayed TBE-vaccine booster
- 2012
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 30:3, s. 499-502
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Tidskriftsartikel (refereegranskat)abstract
- Information is scarce regarding the antibody response when TBE-vaccine booster doses are delayed, which is a common situation in daily life. We have investigated the immune response after a delayed booster dose compared to a normal booster interval in an every-day setting. Overall, 250/260 (96%) of the study participants had neutralizing antibodies post-booster, with no significant difference between normal and delayed booster intervals. Based on our findings we propose that healthy individuals who have failed adherence to the recommended schedule of TBE-vaccination can be given a delayed dose without concern of immunogenicity.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Balogun, Halima A., et al.
(författare)
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Immunogenicity and antigenic properties of Pf332-C231, a fragment of a non-repeat region of the Plasmodium falciparum antigen Pf332
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:1, s. 90-97
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Tidskriftsartikel (refereegranskat)abstract
- Antigen Pf332, a megadalton protein has been shown to be associated with the membrane of infected erythrocytes. Detailed functional studies on the antigen have remained hampered by the cross-reactive nature of antibodies generated to Pf332. Pf332-C231, identified in the C-terminal region of Pf332 was cloned and antibodies against the C231 fragment were shown to react with intact Pf332 antigen by both immunofluorescence and immunoblotting analyses. Antibodies to C231 inhibited in vitro Plasmodium falciparum growth efficiently. In addition, human sera from malaria-exposed individuals reacted with recombinant C231. We show that Pf332-C231 represents a functional domain and is expected to facilitate further studies on Pf332 as a potential target for protective immune responses and the function of the antigen.
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| 22. |
- Balogun, Halima A., et al.
(författare)
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Pf332-C231-reactive antibodies affect growth and development of intra-erythrocytic Plasmodium falciparum parasites
- 2011
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 30:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- The Plasmodium falciparum antigen 332 (Pf332), is a megadalton parasite protein expressed at the surface of infected red cells during later stages of the parasite's developmental cycle. Antibodies to different parts of this antigen have been shown to inhibit parasite growth and adherence to host cells with or without ancillary cells. However, the mechanisms involved in these inhibitions remain largely unknown. We further analysed the activities of specific antibodies with regard to their specific mechanisms of action. For these analyses, affinity purified human antibodies against epitopes in the C-terminal fragment of Pf332 (Pf332-C231) were employed. All purified antibodies recognized Pf332-C231 both by immunofluorescence and ELISA. IgG was the main antibody isotype detected, although all sera investigated had varying proportions of IgG and IgM content. All the antibodies showed a capacity to inhibit parasite growth in P. falciparum cultures to different extents, mainly by acting on the more mature parasite stages. Morphological analysis revealed the antibody effects to be characterized by the presence of a high proportion of abnormal schizonts (15-30%) and pyknotic parasites. There was also an apparent antibody effect on the red cell integrity, as many developing parasites (up to 10% of trophozoites and schizonts) were extracellular. In some cases, the infected red cells appeared to be disintegrating/fading, staining paler than surrounding infected and uninfected cells. Antigen reversal of inhibition confirmed that these inhibitions were antigen specific. Furthermore, the growth of parasites after 22-42 h exposure to antibodies was investigated. Following the removal of antibody pressure, a decreased growth rate of these parasites was seen compared to that of control parasites. The present study confirms the potential of Pf332 as a target antigen for parasite neutralizing antibodies, and further indicates that epitopes within the C231 region of Pf332 should constitute important tools in the dissection of the role of Pf332 in the biology of the malaria parasite, as well as in the design of a malaria vaccine.
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| 23. |
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| 24. |
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| 25. |
- Björkstén, Bengt, 1940-
(författare)
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Diverse microbial exposure : Consequences for vaccine development
- 2012
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Ingår i: Vaccine. - Oxon, United Kingdom : Elsevier. - 0264-410X .- 1873-2518. ; 30:29, s. 4336-4340
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Forskningsöversikt (refereegranskat)abstract
- Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.
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| 26. |
- Blom, Anna, et al.
(författare)
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Contribution of interactions between complement inhibitor C4b-binding protein and pathogens to their ability to establish infection with particular emphasis on Neisseria gonorrhoeae.
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26 Suppl 8, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- Complement activation and resulting opsonisation with C3b form key arms of the innate immune defense against infections. However, a wide variety of pathogens subvert complement attack by binding host complement inhibitors, which results in diminished opsonophagocytosis and killing of bacteria by lysis. Human C4b-binding protein (C4BP) binds Neisseria gonorrhoeae and Streptococcus pyogenes, both uniquely human pathogens. This binding specificity is circumvented by other bacterial species, which bind C4BP from numerous mammalian hosts that they infect. Binding of C4BP to Neisseria is mediated by outer membrane porin proteins and appears to be one of the main factors mediating serum resistance. Targeting C4BP binding sites on bacterial surfaces with vaccine-induced antibodies may block binding of C4BP and enhance a common vaccine design strategy that depends on the generation of complement-dependent bactericidal and opsonophagocytic antibody activities.
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| 27. |
- Blom, Hans, et al.
(författare)
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Flocculate removal after alkaline lysis in plasmid DNA production.
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 29:1, s. 6-10
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Tidskriftsartikel (refereegranskat)abstract
- Alkaline lysis is the most commonly used method following harvest of bacterial cells for production of plasmid DNA. The method was originally developed for laboratory scale experiments and has shown to be challenging at larger scales. A major problem prior to further downstream processing is the risk of filter clogging without efficient removal of the flocculate that occurs after neutralization. For this purpose we here present a scalable method where the clarification of alkaline lysate is greatly simplified. Through a rapid procedure, involving the addition of ammonium hydrogen carbonate to the neutralized alkaline lysate, the flocculate is lifted to the surface of the solution by the released carbon dioxide and ammonium. After this step a clarified solution can be drained from the bottom of the vessel. The procedure does not impact pH, plasmid DNA concentration or the ratio of open circular to supercoiled plasmid DNA in the solution.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Brave, Andreas, et al.
(författare)
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Induction of HIV-1-specific cellular and humoral immune responses following immunization with HIV-DNA adjuvanted with activated apoptotic lymphocytes
- 2010
-
Ingår i: VACCINE. - : Elsevier Science B.V.. - 0264-410X .- 1873-2518. ; 28:9, s. 2080-2087
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Tidskriftsartikel (refereegranskat)abstract
- Delivery of DNA encoding foreign antigens into mammalian cells can induce adaptive immune responses. There are currently many DNA-based vaccines in clinical trials against infectious diseases and cancer but there is a lack of adjuvants for improvement of responses to DNA-based vaccines. Here, we show augmented systemic and mucosa-associated B cell responses after immunization with a cocktail of seven different plasmids (3 env, 2 gag, 1 rev, 1 RT) combined with mitogen activated apoptotic syngeneic lymphocytes in mice. In addition we show that apoptotic cells can function as adjuvant for induction of cellular immune responses in a magnitude comparable to the cytokine adjuvant GM-CSF in mice. These data suggest that activated apoptotic lymphocytes can act independent as adjuvants to improve antigen-specific DNA vaccines.
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| 35. |
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| 36. |
- Brodszki, Nicholas, et al.
(författare)
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Immune responses following meningococcal serogroups A, C, Y and W polysaccharide vaccination in C2-deficient persons: Evidence for increased levels of serum bactericidal antibodies.
- 2015
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 33:15, s. 1839-1845
-
Tidskriftsartikel (refereegranskat)abstract
- Complement C2 deficiency (C2D) is associated with immunological diseases and increased susceptibility to invasive infections caused by encapsulated bacteria such as Neisseria menigitidis. In this study we evaluate the immunogenicity of vaccination against N. menigitidis in C2D. C2D patients (n=22) and controls (n=52) were given a tetravalent meningococcal polysaccharide vaccine. Serum bactericidal antibody (SBA) titres (serogroups A, C, Y and W) were analysed using a rabbit complement source. Levels of IgG, IgM, and IgA, factor B, and factor H, polymorphisms of MBL and Fc-gamma receptors were determined. The C2D patients responded with an increased SBA titre to all four serogroups (p<0.001). The response rates define as SBA titres ≥8 were found to be between 85.7% and 92.5%. The post-vaccination titres for serogroups C, Y and W were equal to healthy controls. C2D patients with a history of invasive infection had a lower post-vaccination SBA titres both compared to healthy C2D persons (p=0.03) and compared to controls (p<0.0001). We found that the G2M*n/G2M*n genotype were associated with a higher SBA titres after immunization (p=0.03). None of the other investigated immunological factors appear to be important in influencing the vaccine responses. Autoimmune diseases in C2D did not affect the vaccine response. In general, vaccination against meningococci gave rise to antibody responses in the C2D patients that equal healthy controls. The response rate was lower to serogroup A and among C2D patients with history of invasive infections. The presence of G2M*n/G2M*n genotype was associated with higher SBA titres after immunization.
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| 37. |
- Broos, Sissela, et al.
(författare)
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Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy.
- 2010
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28, s. 5075-5085
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Tidskriftsartikel (refereegranskat)abstract
- Novel adjuvants and antigen-delivery systems with immunomodulatory properties that shift the allergenic Th2 response towards a Th1 or regulatory T cell response are desired for allergen-specific immunotherapy. This study demonstrates that 200-nm sized biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). gamma-PGA NPs are efficiently internalized by immature MoDCs and strongly stimulate production of chemokines and inflammatory cytokines as well as up-regulation of co-stimulatory molecules and immunomodulatory mediators involved in efficient T cell priming. Furthermore, MoDCs from allergic subjects stimulated in vitro with a mixture of gamma-PGA NPs and extract of grass pollen allergen Phleum pratense (Phl p) augment allergen-specific IL-10 production and proliferation of autologous CD4(+) memory T cells. Thus, gamma-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy.
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| 38. |
- Bråve, Andreas, et al.
(författare)
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Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses
- 2008
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:40, s. 5075-5078
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Tidskriftsartikel (refereegranskat)abstract
- One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity. © 2008 Elsevier Ltd. All rights reserved.
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| 39. |
- Bråve, Andreas, et al.
(författare)
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Maternal immune status influences HIV-specific immune responses in pups after DNA prime protein boost using mucosal adjuvant
- 2008
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:47, s. 5957-5966
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to determine the impact of maternal HIV-1 specific immunity on HIV-DNA immunization of 2 weeks old pups during the breast-feeding period. Adult female mice received intranasal or intradermal HIV DNA (gp160Env, p37Gag, Nef, Tat and Rev) prime and recombinant protein booster immunizations that induced mucosal and systemic HIV-1 specific B and T cell responses. Intranasal administration of the immunogens induced higher serum IgG titers to HIV antigens than the intradermal immunization. Furthermore, predominantly higher HIV-1 specific fecal IgA titers were obtained in nasally immunized mice. The capacity to respond to one single prime with DNA and one boost with recombinant protein was then compared in pups born to mothers displaying HIV-1-specific immune responses and in pups born to non-vaccinated mothers. Immune responses to the greatest number of antigens were detected in pups born to mothers having the highest HIV-1 specific immune responses. These data suggest that HIV-1 DNA-plasmid immunization during breast-feeding and recombinant protein boosting shortly thereafter enhances the breadth of the humoral HIV-1 specific immune responses.
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| 40. |
- Bucht, Göran, et al.
(författare)
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Modifying the cellular transport of DNA-based vaccines alters the immune response to hantavirus nucleocapsid protein
- 2001
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Ingår i: Vaccine. - 0264-410X .- 1873-2518. ; 19:28-29, s. 3820-3829
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus is a member of the hantavirus genus (family Bunyaviridae) and is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS) in Europe. A genetic vaccination approach was conducted to investigate if the immune response could be modulated using different cellular secretion and/or localisation signals, and the immune responses were analysed in BALB/c mice and in a bank vole infectious model. Rodents vaccinated with DNA constructs encoding the antigen fused to an amino-terminal secretion signal raised significantly higher antibody levels when compared to using constructs lacking secretion signals. Furthermore, the ratios of the IgG subclasses (IgG2a/IgG1) were raised by the use of cellular localisation signals, indicating a more pronounced Th1-type of immune response. The majority of the mice, or bank voles, immunised with DNA encoding a secreted form of the antigen showed a positive lymphoproliferative response and were protected against challenge with Puumala virus (strain Kazan-wt).
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| 41. |
- Buonaguro, L, et al.
(författare)
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DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity
- 2007
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 25:32, s. 5968-5977
-
Tidskriftsartikel (refereegranskat)abstract
- The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3. © 2007 Elsevier Ltd. All rights reserved.
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| 42. |
- Byström, Emma, et al.
(författare)
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Parental attitudes and decision-making regarding MMR vaccination in an anthroposophic community in Sweden – A qualitative study
- 2014
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 32:50, s. 6752-6757
-
Tidskriftsartikel (refereegranskat)abstract
- Measles outbreaks occur regularly throughout Europe, up to 31500 cases in the previous year, particularly where there are pockets of populations with lower vaccination coverage than the recommended ≥95%. Anthroposophic communities in Europe are one of several groups with relatively low vaccination coverage. In Sweden, outbreaks of measles and rubella were reported from an anthroposophic community. Thus the aim of this qualitative study was to explore facilitators and barriers to MMR vaccination among parents living in anthroposophic communities in Sweden. Twenty parents living in an anthroposophic community were interviewed, focusing on their views and decisions on MMR vaccination. The interviews were analyzed using qualitative content analysis. Two overarching views of health emerged, differentiating broadly parents who vaccinate vs. parents who do not vaccinate. Four themes describing parental attitudes toward measles vaccination were developed and three of these, the conformers, the pragmatists and the attentive delayers describe different approaches toward vaccinations among those who actually vaccinate. The last theme, promoters of natural immunity, represents those postponing or refusing vaccination beyond childhood. This study suggests that there is a spectrum of parental beliefs regarding MMR vaccination in this anthroposophic community. Interventions specifically targeted to the anthroposophic community and strengthening health workers capacity for a constructive dialog on vaccine's benefit and risks may contribute to higher vaccination coverage. This is believed to minimize the risk of future epidemics and contribute to the WHO European Region's goal of eliminating measles.
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| 43. |
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| 44. |
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| 45. |
- Cano, F., et al.
(författare)
-
Partial protection to respiratory syncytial virus (RSV) elicited in mice by intranasal immunization using live staphylococci with surface-displayed RSV-peptides
- 2000
-
Ingår i: Vaccine. - 0264-410X .- 1873-2518. ; 18:24, s. 2743-2752
-
Tidskriftsartikel (refereegranskat)abstract
- A live bacterial vaccine-delivery system based on the food-grade bacterium Staphylococcus carnosus was used for delivery of peptides from the G glycoprotein of human respiratory syncytial virus, subtype A (RSV-A). Three peptides, corresponding to the G protein amino acids, 144-159 (denoted G5), 190-203 (G9) and 171-188 (G4 S), the latter with four cysteine residues substituted for serines, were expressed by recombinant means as surface-exposed on three different bacteria, and their surface accessibility on the bacteria was verified by fluorescence-activated cell sorting (FACS). Intranasal immunization of mice with the live recombinant staphylococci elicited significant anti-peptide as well as anti-virus serum IgG responses of balanced IgG1/IgG2a isotype profiles, and upon viral challenge with 10(5) tissue culture infectious doses(50) (TCID50), lung protection was demonstrated for approximately half of the mice in the G9 and G4 S immunization groups. To our knowledge, this is the first study in which protective immunity to a viral pathogen has been evoked using food-grade bacteria as vaccine-delivery vehicles.
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| 46. |
- Carlsson, Fredrika, et al.
(författare)
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Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon immunization with different cytomegalovirus candidate vaccines.
- 2007
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein B (gB) is a major component in several vaccines that are under development for prevention of disease by cytomegalovirus. It contains multiple determinants that are targets for neutralizing antibodies. One of them is site I of antigenic domain 2 (AD-2). The epitope, defined by short peptides, is quite conserved between different isolates. However, it is poorly immunogenic in natural infection. In this study we investigated the extent to which different vaccines, attenuated live Towne vaccine with or without priming with a canarypox virus coding for gB, or a recombinant gB vaccine adjuvanted with MF59, induced antibodies to this epitope. As in natural infection only a fraction of all subjects developed antibody responses against site I of AD-2 following vaccination. We suggest that strategies that enhance immunogenicity of this epitope will improve vaccine efficacy.
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| 47. |
- Carlsson, Rose-Marie, et al.
(författare)
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Control of pertussis--lessons learnt from a 10-year surveillance programme in Sweden.
- 2009
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 27:42, s. 5709-18
-
Tidskriftsartikel (refereegranskat)abstract
- Sweden was the only country in the world without any general pertussis vaccination when acellular pertussis (aP) vaccines were introduced. Since 1996 aP vaccines are given at the ages of 3, 5 and 12 months, with a 99% coverage, and until 2007 without a later booster. The long-term effects of aP vaccines, monitored within an enhanced surveillance project, were discussed at an international workshop in Stockholm in November 2008. The unique Swedish experience demonstrates that aP vaccines are capable of achieving the primary goal of a national vaccination programme, i.e., to significantly reduce the burden of pertussis in pre-school children. Throughout the 10-year surveillance period the highest age-specific incidence was reported in unvaccinated infants or those who had received only one dose, with most hospitalisations in this age group and eight deaths among unvaccinated infants. Complementary strategies are needed to achieve further reduction in morbidity from circulation of Bordetella pertussis.
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| 48. |
- Carlsson, Rose-Marie, et al.
(författare)
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Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years
- 2015
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 33:31, s. 3717-3725
-
Tidskriftsartikel (refereegranskat)abstract
- Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 mu g) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 mu g). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. (C) 2015 Elsevier Ltd. All rights reserved.
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| 49. |
- Chen, I-Hua, et al.
(författare)
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Adapting the Motors of Influenza Vaccination Acceptance Scale into the Motors of COVID-19 Vaccination Acceptance Scale : Psychometric evaluation among mainland Chinese university students
- 2021
-
Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 39:32, s. 4510-4515
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Tidskriftsartikel (refereegranskat)abstract
- Background: COVID-19 continues to ravage the world with economies and life significantly and negatively affected. Fortunately, there has been significant progress in the production of vaccines to stem the infection. However, with controversies and myths surrounding vaccinations, it is timely to examine individuals’ willingness to vaccinate. The present study adapted the Motors of Influenza Vaccination Acceptance Scale (MoVac-Flu Scale) into the Motors of COVID-19 Vaccination Acceptance Scale (MoVac-COVID19S) for validation and assessed the acceptance of COVID-19 vaccination utilizing the cognitive model of empowerment (CME).Methods: A total of 3145 university students (mean age = 20.80 years; SD = 2.09) were recruited for the present study between January 5 and 16, 2021. Two MoVac-COVID19S scales (9-item and 12-item) were adapted from the MoVac-Flu Scale, an instrument developed using CME. Psychometric tests were conducted to ascertain reliability and validity properties.Results: The findings indicated that the MoVac-COVID19S had high internal consistency in both the 9-item version (ω = 0.921) and 12-item version (ω = 0.898). The factor structure of the MoVac-COVID19S (9-item and 12-item versions) corresponded well with CME theory. All the fit indices were satisfactory (comparative fit index = 0.984, Tucker-Lewis index = 0.971, root mean square error of approximation = 0.088, standardized root mean square residual = 0.058) but the 9-item MoVac-COVID had better fit indices than the 12-item MoVac-COVID due to the negative wording effects existing in the 12-item MoVac-COVID19S. The scale had satisfactory known-group validity in both 9-item and 12-item versions.Conclusions: The MoVac-COVID19S has promising psychometric properties based on internal consistency, factor structure, and known-group validity.
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| 50. |
- Cheng, Chunmei, et al.
(författare)
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Induction of protective immunity by vaccination against Chlamydia trachomatis using the major outer membrane protein adjuvanted with CpG oligodeoxynucleotide coupled to the nontoxic B subunit of cholera toxin.
- 2009
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 27:44, s. 6239-46
-
Tidskriftsartikel (refereegranskat)abstract
- The present study was undertaken to test the efficacy of immunization with the native major outer membrane protein (nMOMP) of Chlamydia trachomatis mouse pneumonitis (MoPn) serovar in combination with a novel immunostimulatory adjuvant consisting of CpG oligodeoxynucleotide (ODN) linked to the nontoxic B subunit of cholera toxin (CTB-CpG) to elicit a protective immune response to C. trachomatis. High levels of Chlamydia-specific IgG antibodies were detected in the sera from BALB/c mice immunized intramuscularly and subcutaneously (i.m.+s.c.) with the nMOMP/CTB-CpG vaccine or with nMOMP adjuvanted with a mixture of CT and CpG ODN (CT+CpG). Further, these immunization schemes gave rise to significant T-cell-mediated Chlamydia-specific immune responses. No Chlamydia-specific humoral or cell-mediated immune responses were detected in the control mice vaccinated with ovalbumin together with either CTB-CpG or CT+CpG. Following an intranasal challenge with C. trachomatis the groups of mice immunized with nMOMP plus CTB-CpG, CT+CpG or live C. trachomatis were found to be protected based on their change in body weight and lung weight as well as number of inclusion forming unit recovered from the lungs, as compared with control groups immunized with ovalbumin plus either adjuvants. Interestingly, IFN-gamma-producing CD4(+), but not CD8(+), T-cells showed a significant correlation with the outcomes of the challenge. In conclusion, nMOMP in combination with the novel adjuvant CTB-CpG elicited a significant antigen-specific antibody and cell-mediated immune responses as well as protection against a pulmonary challenge with C. trachomatis.
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