| 1. |
- Eriksson, Fredrik, et al.
(författare)
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DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:37, s. 3843-3848
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Tidskriftsartikel (refereegranskat)abstract
- We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment. Vaccine doses ranged from 50 to 1600 mu g. Study subjects received five vaccinations at four week intervals. All patients have had at least one year of follow-up. No systemic toxicity was observed. Discomfort from electroporation did not require analgesia or topical anesthetic. No clinically significant changes in PSA kinetics were observed as all patients required antiandrogen therapy shortly after completion of the 5 months of vaccination due to rising PSA. Immunogenicity, as measured by T-cell reactivity to the modified PSA peptide and to a mix of overlapping PSA peptides representing the full length protein, was observed in some patients. All but one patient had pre-study PSA specific T-cell reactivity. ADT alone resulted in increases in T-cell reactivity in most patients. Intradermal vaccination with skin electroporation is easily performed with only minor discomfort for the patient. Patients with biochemical relapse of prostate cancer are a good model for testing immune therapies.
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| 2. |
- Falkeborn, Tina, et al.
(författare)
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Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants : cholera toxin and alum
- 2015
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Ingår i: Jacobs Journal of Vaccine and Vaccination. - : Jacobs Publishers. - 2381-2664. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.
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| 3. |
- Falkeborn, Tina, et al.
(författare)
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The intranasal adjuvant Endocine((TM)) enhances both systemic and mucosal immune responses in aged mice immunized with influenza antigen
- 2017
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Ingår i: Virology Journal. - : BioMed Central (BMC). - 1743-422X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Despite availability of annual influenza vaccines, influenza causes significant morbidity and mortality in the elderly. This is at least in part a result of immunosenescence; the age-dependent decrease in immunological competence that results in greater susceptibility to infections and reduced responses to vaccination. To improve protective immune responses in this age group, new vaccines strategies, such as the use of adjuvants, are needed. Here, we evaluated the mucosal vaccine adjuvant Endocine(TM), formulated with split influenza antigen and administered intranasally in aged (20-month old) mice. Humoral immune responses were assessed and compared to unadjuvanted intranasal and subcutaneous vaccines. We show that formulation with Endocine(TM) significantly enhances hemagglutination inhibition (HI) titers, as well as serum IgG and mucosal IgA antibody titers, compared to both types of unadjuvanted vaccines. Thus, our results indicate that intranasal vaccination with Endocine(TM) is a possible approach for the development of mucosal influenza vaccines for the elderly.
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| 4. |
- Falkeborn, Tina, et al.
(författare)
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The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged mice
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.
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| 5. |
- Maltais, Anna-Karin, et al.
(författare)
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Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 32:26, s. 3307-15
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Tidskriftsartikel (refereegranskat)abstract
- Influenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. There is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. Endocine™ is a lipid-based mucosal adjuvant composed of endogenous lipids found ubiquitously in the human body. Intranasal administration of influenza antigens mixed with this adjuvant has been shown to induce local and systemic immunity as well as protective efficacy against homologous influenza virus challenge in mice. Here we used ferrets, an established animal model for human influenza virus infections, to further investigate the potential of Endocine™ as an adjuvant. Intranasal administration of inactivated pandemic H1N1/California/2009 split antigen or whole virus antigen mixed with Endocine™ induced high levels of serum hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers that were also cross reactive against distant swine viruses of the same subtype. HI and VN antibody titers were already demonstrated after a single nasal immunization. Upon intratracheal challenge with a homologous challenge virus (influenza virus H1N1/The Netherlands/602/2009) immunized ferrets were fully protected from virus replication in the lungs and largely protected against body weight loss, virus replication in the upper respiratory tract and pathological changes in the respiratory tract. Endocine™ formulated vaccines containing split antigen induced higher HI and VN antibody responses and better protection from body weight loss and virus shedding in the upper respiratory tract than the Endocine™ formulated vaccine containing whole virus antigen.
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