Genetic background impacts vaccine-induced reduction of pneumococcal colonization

Abstract

a b s t r a c tVaccination has been one of the most successful strategies to reduce morbidity and mortality caused by respiratory infections. Recent evidence suggests that differences in the host genetic background and environmental factors may contribute to heterogeneity in the immune response to vaccination. During preclinical testing, vaccines are often evaluated in a single mouse inbred strain, which may not translate well to the heterogeneous human population. Here, we examined the influence of host genetic background on vaccine-induced protection against pneumococcal colonization in two commonly used inbred mouse strains, i.e. C57BL/6 and BALB/c as well as the F1 cross of these two strains. Groups of mice were vaccinated intranasally with a vaccine formulation containing a model pneumococcal antigen, i.e. pneumococcal surface protein A (PspA), adjuvanted with cholera toxin subunit B (CTB). Even in the absence of vaccination, differences in colonization density were observed between mouse strains. Although vaccination significantly reduced pneumococcal density in all mouse strains, differences were observed in the magnitude of protection. We therefore examined immunological parameters known to be involved in vaccine-induced mucosal clearance of S. pneumoniae. We found that PspA-specific IgG levels in nasal tissue differed between mouse strains, but in all cases it correlated significantly with a reduction in colonization. Furthermore, increased mucosal IL17A, but not IFNc, IL10, or IL4, was found to be mouse strain specific. This suggests that the reduction of bacterial load may be accompanied by a Th17 response in all genetic backgrounds, although the cytokine dynamics may differ. Increased insight into the different immune mechanisms that affect pneumococcal carriage will contribute to development of future vaccines against S. pneumoniae

Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs

“…In addition, since mucosal IgA was not measured, it is difficult to state whether there was a failure of induction of mucosal antibodies to these proteins or a failure of antibodies to prevent colonization. The impact of immunization on the reduction of the colonization load by pneumococcus in a mouse model was found to be dependent on individual host factors as well as vaccine-associated factors (34). There was a reduction in the incidence of systemic disease in vaccinated animals, which could have been due to reduced colonization and invasion or an increase in bactericidal/opsonic antibodies, or both.…”

Influence of gut microbiota on mucosal IgA antibody response to the polio vaccine

“…Our study had limitations. Some other factors, such as genetic factors, have been attributed to mucosal antibody responses [46][47][48] . Unfortunately, in this study, individual genetic differences were not examined because of restrictions imposed by the sampling requirements.…”

High-resolution quantitative proteomics applied to the study of the specific protein signature in the sputum and saliva of active tuberculosis patients and their infected and uninfected contacts

“…Remarkably, many individuals in close contact with an active TB patient do not become infected. Increasing evidence suggests that genetic heterogeneity of the host affects immune response to intracellular pathogens, such as mycobacteria (9)(10)(11). Innate immune response is the first line of defense and plays a key role in the quality, strength and efficacy of the adaptive immune response (12).…”