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Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

ABSTRACT: Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F.

SUBMITTER: Zengel J

PROVIDER: S-EPMC5785236 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

Zengel James J Phan Shannon I SI Pickar Adrian A Xu Pei P He Biao B

Vaccine 20170613 32

Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China ...[more]

PMID: 28623030

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Project description:With the implementation of mumps virus (MuV) vaccination in the expanded program on immunization (EPI) in mainland China since 2008, the incidence of mumps has decreased, and the natural epidemic pattern of mumps has slightly changed during 2013-2015. The two epidemic peaks (April-July and November-December) became less obvious than those observed from 2004 to 2012. Children and adolescents younger than 15, particularly in the five-to-nine-year-old age group, remain the target group and should be the focus of high-quality immunization activities in mainland China. However, it was also found that the incidence and reported cases of mumps decreased in each age group during 2013-2015, particularly in the five-to-nine-year-old and ten-to-fourteen-year-old age groups. The proportion of mumps cases among adults in some provinces also increased. Unlike the changes in the epidemiological characteristics of mumps affected by vaccination, the data of MuV virology surveillance indicated that most of the MuV transmission chains have not yet been effectively interrupted, and MuV remains a natural epidemic pattern in mainland China. In the MuV virology surveillance, 194 MuV strains during 2013-2015 were isolated from 10 of 31 provinces in mainland China. Based on the phylogenetic analysis of the small hydrophobic (SH) gene, both genotype F (99.0%) and G (1.0%) were identified, and genotype F was still the predominant genotype continuously circulating in mainland China. Representative genotype F and G strains isolated in China from 1995 to 2012 were selected for further analysis. The results indicated that there were multiple transmission chains within genotype F, with no obvious geographical or time differences. The high genetic diversity of genotype F strains could be a result of the continuous transmission and evolution of the MuV in mainland China. Genotype G was also detected in four provinces in mainland China. Because of the limited epidemiological data, it was uncertain whether the genotype G MuV strains found in 2011 and 2013 were imported from other countries. Therefore, combined high-quality epidemiological and virological surveillance is necessary for mumps control; it can also be used to observe the changes in epidemiological characteristics and viral transmission of mumps over time after mumps-containing vaccine (MuCV) implementation and to provide a comprehensive epidemiological and genetic baseline for mumps elimination in mainland China.

Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States.MethodsIn an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose.ResultsA total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples.ConclusionsThe safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2-3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

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Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

Publications

Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

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