Establishment of an adult mouse model for direct evaluation of the efficacy of vaccines against Vibrio cholerae

• We describe here a new animal model that offers the prospect of using conventional adult mice for direct evaluation of the protective potential of new cholera vaccines. Pretreatment of adult mice with oral streptomycin allowed intestinal colonization by streptomycin-resistant Vibrio cholerae strains of either the O1 or the O139 serogroup. Bacteria were recovered in greatest numbers from the cecum and large intestine, but recoveries from all regions of the gut correlated significantly with bacterial excretion in fresh fecal pellets, which thus provides a convenient indicator of the extent and duration of gut colonization. Mice immunized mucosally or systemically with viable or inactivated V. cholerae were shown to be comparatively refractory to colonization after challenge with the immunizing strain. Several variables were examined to optimize the model, the most significant being the size of the challenge inoculum; surprisingly, a smaller challenge dose resulted in more consistent and sustained colonization. Studies with mutant strains unable to produce cholera toxin or toxin-coregulated pili revealed that neither factor contributed significantly to colonization potential. Protection against V. cholerae challenge was shown to be serogroup restricted, and significant inverse correlations were detected between serum and intestinal anti-lipopolysaccharide antibody responses and the levels of excretion of challenge organisms. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

cholera toxin

cholera vaccine

lipopolysaccharide

streptomycin

animal experiment

animal model

animal tissue

article

bacterial colonization

bacterial strain

bacterium pilus

cecum

cholera

controlled study

drug efficacy

female

immune response

immunization

inoculation

large intestine

mouse

nonhuman

priority journal

Vibrio cholerae

Animals

Anti-Bacterial Agents

Antibodies

Bacterial

Cholera Vaccines

Colony Count

Microbial

Disease Models

Animal

Drug Resistance

Bacterial

Feces

Intestine

Large

Mice

Mice

Inbred BALB C

Mucous Membrane

Vibrio cholerae O1

Vibrio cholerae O139

Animals

Anti-Bacterial Agents

administration & dosage

Antibodies

Bacterial

analysis

blood

Cecum

microbiology

Cholera

prevention & control

Cholera Vaccines

immunology

Colony Count

Microbial

Disease Models

Animal

Drug Resistance

Feces

Female

Intestine

Large

Mice

Inbred BALB C

Mucous Membrane

Streptomycin

Vibrio cholerae O1

drug effects

growth & development

Vibrio cholerae O139

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)