Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain

Caro-Aguilar, Ivette; Indrawati, Lani; Kaufhold, Robin M.; Gaunt, Christine; Zhang, Yuhua; Nawrocki, Denise K.; Giovarelli, Cecilia; Winters, Michael A.; Smith, William J.; Heinrichs, Jon H.; Skinner, Julie M.

doi:10.1016/j.vaccine.2016.12.055

Cited by 21 publications

(13 citation statements)

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“…Pneumococcal multiplexed opsonophagocytosis assays (MOPA) were performed as described previously [ 21 , 22 ] . Following the incubation of mixture of antibody, bacteria, complement (Pel-Freez Biologicals) and HL-60 cell (ATCC), 10 μl reaction was transferred to an individual well on a Costar (Corning) or Millipore 96-well filter plate, 100 μl THYE broth (Todd Hewitt Yeast Extract medium, Teknova) was added to each well.…”

Section: Methodsmentioning

confidence: 99%

Human monoclonal antibodies isolated from a primary pneumococcal conjugate Vaccinee demonstrates the expansion of an antigen-driven Hypermutated memory B cell response

et al. 2018

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BackgroundCommunity-acquired pneumonia is a leading infectious cause of hospitalization. A few vaccines exist to prevent pneumococcal disease in adults, including a pneumococcal polysaccharide unconjugated vaccine and a protein conjugated polysaccharide vaccine. Previous studies on the human immune response to the unconjugated vaccine showed that the vaccine boosted the existing memory B cells. In the present study, we investigated the human B cell immune response following pneumococcal polysaccharide conjugate vaccination.MethodsPlasmablast B cells from a pneumococcal polysaccharide conjugate vaccinee were isolated and cloned for analysis. In response to primary vaccination, identical sequences from the plasmablast-derived antibodies were identified from multiple B cells, demonstrating evidence of clonal expansion. We evaluated the binding specificity of these human monoclonal antibodies in immunoassays, and tested there in vitro function in a multiplexed opsonophagocytic assay (MOPA). To characterize the plasmablast B cell response to the pneumococcal conjugated vaccine, the germline usage and the variable region somatic hypermutations on these antibodies were analyzed. Furthermore, a serotype 4 polysaccharide-specific antibody was tested in an animal challenge study to explore the in vivo functional activity.ResultsThe data suggests that the pneumococcal polysaccharide conjugate vaccine boosted memory B cell responses, likely derived from previous pneumococcal exposure. The majority of the plasmablast-derived antibodies contained higher numbers of variable region somatic hypermutations and evidence for selection, as demonstrated by replacement to silent ratio’s (R/S) greater than 2.9 in the complementarity-determining regions (CDRs). In addition, we found that VH3/JH4 was the predominant germline sequence used in these polysaccharide-specific B cells. All of the tested antibodies demonstrated narrow polysaccharide specificity in ELISA binding, and demonstrated functional opsonophagocytic killing (OPK) activity in the MOPA assay. The in-vivo animal challenge study showed that the tested serotype 4 polysaccharide-specific antibody demonstrated a potent protective effect when administered prior to bacterial challenge.ConclusionsThe findings on the pneumococcal polysaccharide conjugate vaccine responses from a vaccinated subject reported in this study are similar to previously published data on the pneumococcal polysaccharide unconjugated vaccine responses. In both vaccine regimens, the pre-existing human memory B cells were expanded after vaccination with preferential use of the germline VH3/JH4 genes.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3517-7) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Human monoclonal antibodies isolated from a primary pneumococcal conjugate Vaccinee demonstrates the expansion of an antigen-driven Hypermutated memory B cell response

et al. 2018

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“…However, it is not clear why the net benefit of PCVs vary within the same population where exposure is more consistent between risk groups. Understanding variations in the net benefit of PCVs against IPD in different risk groups is important as PCVs with expanded numbers of serotypes are developed and deployed [10].…”

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Differences in the Impact of Pneumococcal Serotype Replacement in Individuals With and Without Underlying Medical Conditions

Weinberger

Warren

Dalby

et al. 2018

Clinical Infectious Diseases

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Background. Pneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD). However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to nonvaccine serotypes (NVTs). The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain comorbidities, following the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood vaccination program in Denmark. Methods. We used nationwide surveillance data for IPD and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends. Results. Following the introduction of PCV7 and PCV13 in children, the net impact of serotype replacement varied considerably by age group and comorbidities. Differences in the magnitude of serotype replacement were due to variations in the incidence of NVTs in the different risk groups before the introduction of PCVs. The relative increases in the incidence of IPD caused by specific NVTs did not differ appreciably between risk groups in the postvaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the NVTs comprised a larger proportion of cases prior to the introduction of the vaccines. Conclusions. These findings could help to predict the impact of next-generation PCVs in specific risk groups. Keywords. pneumococcus; serotype replacement; conjugate vaccines; Bayesian hierarchical model. Pneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD) worldwide [1-5]. Because PCVs interrupt transmission of pneumococcus among healthy children, the introduction of PCVs has led to reductions in the incidence of IPD among both vaccinated children and (indirectly) among unvaccinated adults [1, 6]. A meta-analysis of data from the United States, Europe, and Australia found that, on average, IPD due to serotypes in the 7-valent PCV (PCV7) declined by approximately 90% among adults [1]. However, these declines in IPD due to vaccine-targeted serotypes (VTs) were at least partially offset by increases in IPD caused by nonvaccine serotypes (NVTs), a phenomenon known as serotype replacement [1, 7]. The net benefit of PCVs is therefore determined by both

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“…Three doses containing 1/20 of the human dose of PCV13 were given to mice subcutaneously in a volume of 100 µL. Dose-response analysis of a similar conjugate vaccine has shown the induction of high antibody titers and protection of mice against a lethal challenge with a 6B strain by the inoculation of three doses of 1/25 of the human dose [39]. Serum was collected two weeks after the third immunization for the evaluation of antibody levels.…”

Section: Immunizationmentioning

confidence: 99%

Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

et al. 2020

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Widespread use of pneumococcal conjugate vaccines (PCVs) has led to substitution of vaccine-type (VT) strains by non-vaccine type (NVT) strains in nasopharyngeal carriage. We compared the efficacy of PCV13 and a nasal protein formulation containing pneumococcal surface protein A (PspA) adjuvanted with the whole-cell pertussis vaccine (wP) in the protection against co-colonization challenge models in mice with VT and NVT strains expressing different PspAs. Immunized mice were challenged with two different mixtures: i. VT4 (PspA3) + NVT33 (PspA1) and ii. VT23F (PspA2) + NVT15B/C (PspA4). Results from the first mixture showed a reduction in loads of VT4 strain in the nasopharynx of mice immunized with PCV13. A statistical difference between the loads of the VT and NVT strains was observed, indicating a competitive advantage for the NVT strain in PCV13-immunized animals. In the second mixture, no reduction was observed for the VT23F strain, probably due to low levels of anti-23F polysaccharide IgG induced by PCV13. Interestingly, a combination of the PspA formulation containing wP with PCV13 led to a reduction in colonization with both strains of the two mixtures tested, similar to the groups immunized nasally with wP or PspA plus wP. These results indicate that a combination of vaccines may be a useful strategy to overcome pneumococcal serotype replacement.

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Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain

Cited by 21 publications

References 23 publications

Human monoclonal antibodies isolated from a primary pneumococcal conjugate Vaccinee demonstrates the expansion of an antigen-driven Hypermutated memory B cell response

Human monoclonal antibodies isolated from a primary pneumococcal conjugate Vaccinee demonstrates the expansion of an antigen-driven Hypermutated memory B cell response

Differences in the Impact of Pneumococcal Serotype Replacement in Individuals With and Without Underlying Medical Conditions

Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

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