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Membrane particles evoke a serotype-independent cross-protection against pneumococcal infection that is dependent on the conserved lipoproteins MalX and PrsA.

ABSTRACT: Pneumococcal conjugate vaccines (PCVs) used in childhood vaccination programs have resulted in replacement of vaccine-type with nonvaccine-type pneumococci in carriage and invasive pneumococcal disease (IPD). A vaccine based on highly conserved and protective pneumococcal antigens is urgently needed. Here, we performed intranasal immunization of mice with pneumococcal membrane particles (MPs) to mimic natural nasopharyngeal immunization. MP immunization gave excellent serotype-independent protection against IPD that was antibody dependent but independent of the cytotoxin pneumolysin. Using Western blotting, immunoprecipitation, mass spectrometry, and different bacterial mutants, we identified the conserved lipoproteins MalX and PrsA as the main antigens responsible for cross-protection. Additionally, we found that omitting the variable surface protein and vaccine candidate PspA from MPs enhanced protective immune responses to the conserved proteins. Our findings suggest that MPs containing MalX and PrsA could serve as a platform for pneumococcal vaccine development targeting the elderly and immunocompromised.

SUBMITTER: Narciso AR

PROVIDER: S-EPMC9191655 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Membrane particles evoke a serotype-independent cross-protection against pneumococcal infection that is dependent on the conserved lipoproteins MalX and PrsA.

Narciso Ana Rita AR Iovino Federico F Thorsdottir Sigrun S Mellroth Peter P Codemo Mario M Spoerry Christian C Righetti Francesco F Muschiol Sandra S Normark Staffan S Nannapaneni Priyanka P Henriques-Normark Birgitta B

Proceedings of the National Academy of Sciences of the United States of America 20220601 23

Pneumococcal conjugate vaccines (PCVs) used in childhood vaccination programs have resulted in replacement of vaccine-type with nonvaccine-type pneumococci in carriage and invasive pneumococcal disease (IPD). A vaccine based on highly conserved and protective pneumococcal antigens is urgently needed. Here, we performed intranasal immunization of mice with pneumococcal membrane particles (MPs) to mimic natural nasopharyngeal immunization. MP immunization gave excellent serotype-independent protec ...[more]

PMID: 35648835

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Project description:Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children <5 years of age by 75%. However, due to replacement through herd effects, the decrease among the older population is predicted to be much less (20-40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including new serotypes in the vaccine (e.g. 22 and 9N).

Project description:BackgroundStreptococcus pneumoniae (pneumococcus) causes invasive pneumococcal disease (IPD) and non-invasive acute respiratory infections (ARIs). Three pneumococcal conjugate vaccines (PCVs) are recommended in the United States with additional products in clinical trials. We aimed to estimate 1) proportions of IPD cases and pneumococcal ARIs caused by serotypes targeted by existing and pipeline PCVs and 2) annual U.S. pneumococcal burdens potentially preventable by PCVs.MethodsWe estimated serotype distribution and proportions of non-invasive pneumococcal ARIs (AOM [children only], sinusitis, non-bacteremic pneumonia) and IPD attributable to serotypes targeted by each PCV using Markov chain Monte Carlo approaches incorporating data from studies of serotype distribution in ARIs and Active Bacterial Core Surveillance (ABCs) data. We then estimated annual numbers of outpatient-managed pneumococcal ARIs, non-bacteremic pneumococcal pneumonia hospitalizations, and IPD cases potentially preventable by PCVs in the United States by multiplying pneumococcal disease incidence rates by PCV-targeted proportions of disease and vaccine effectiveness estimates.ResultsIn children, PCV15, PCV20, PCV24, PCV25, and PCV31 serotypes account for 16% (95% confidence interval: 15-17%), 31% (30-32%), 34% (32-35%), 43% (42-44%), and 68% (67-69%) of pneumococcal acute otitis media cases, respectively. In adults, PCV15, PCV20, PCV21, PCV24, PCV25, and PCV31 serotypes account for 43% (38-47%), 52% (47-57%), 69% (64-73%), 65% (61-70%), 62% (57-67%), and 87% (83-90%) of pneumococcal non-bacteremic pneumonia cases. For IPD, 42-85% of pediatric and 42-94% of adult cases were due to PCV-targeted serotypes. PCV-preventable burdens encompassed 270 thousand-3.3 million outpatient-managed ARIs, 2-17 thousand non-bacteremic pneumonia hospitalizations, and 3-14 thousand IPD cases in the United States annually.ConclusionsAcross pneumococcal conditions, coverage and preventable burdens were lowest for PCV15 and highest for PCV31, with PCV21 also targeting sizeable burdens of adult disease. Serotype distribution across syndromes may inform vaccine formulations and policy.

Dataset Information

Membrane particles evoke a serotype-independent cross-protection against pneumococcal infection that is dependent on the conserved lipoproteins MalX and PrsA.

Publications

Membrane particles evoke a serotype-independent cross-protection against pneumococcal infection that is dependent on the conserved lipoproteins MalX and PrsA.

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