Sera from different age cohorts in Belgium show limited cross-neutralization between the mumps vaccine and outbreak strains

Abstract

Objectives: Mumps used to affect children between 2 and 15 years old. The mumpsemeasleserubella (MMR) vaccine is available, with vaccine coverage rate of about 85% after two vaccine doses. Recently new mumps outbreaks have emerged in highly vaccinated populations; the causes for these new outbreaks are yet unknown. We tested if a difference in seroneutralizing capacity against the vaccine and wild-type viruses existed and if waning immunity could be detected. Methods: In this study, 570 serum samples (age group 2e3 years (n ¼ 96), 8e9 years (n ¼ 95), 13 e14 years (n ¼ 94), 18e20 years (n ¼ 96), 24e26 years (n ¼ 92) and 50 þ years (n ¼ 97)) in Belgium were tested in the rapid fluorescent foci inhibition test for their neutralizing capacity against the vaccine and wild-type viruses. Results: Neutralizing antibodies against the vaccine strain were present in 84% (81/97) of the 2e3-year, 74% (70/95) of the 8e9-year, 81% (76/94) of the 13e14-year, 76% (73/96) of the 18e20-year, 67% (62/92) of the 24e26-year and 77% (75/97) of the 50þ-year age group serum samples. For all age groups, only about half of these serum samples were also positive for the wild-type virus. The geometric mean titres for the vaccine and wild-type virus for all younger age groups, except for 24e26 years, were significantly different, demonstrating poor in vitro cross-neutralization. Conclusions: A possible contribution of antigenic differences between the genotype A and G mumps virus as well as other immune factors, in addition to lower-than-optimal vaccination coverage and waning immunity, could explain the poor in vitro cross-neutralization and should be further studied.

Measles Virus Infection and Immunity in a Suboptimal Vaccination Coverage Setting

“…Reduced efficacy of vaccine-induced immunity against wild type MeV strains has been hypothesized to play a role in measles reemergence [11,38]. In the case of mumps, infection in fully vaccinated individuals are not uncommon, and serum samples from vaccinated individuals have been shown to neutralize the currently circulating mumps virus genotype G less efficiently than other genotypes and the vaccine strain [39,40]. Our study demonstrated that this is not the case for measles.…”

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

“…Cohen et al ( 101 ) also demonstrated minimal antibody level decline after two MMR doses 6–7 years after second vaccination. Neutralizing antibodies against the JL-5 vaccine strain has also been detected in ~80% for age groups 2–20 years, 67% for age group 24–26 years; and 77% for age group 50+ years ( 187 ).…”

“…Vaccination aims to stimulate the host immunological process and formation of cell-mediated immunological memory via the use of live-attenuated or of inactivated/subunit vaccine components to promote a cell-mediated immune response. Extensive knowledge gaps significantly hinder improvements to the mumps vaccine and prospects for mumps eradication and maintaining proficient population immunity ( 3 , 122 , 187 ). Few studies have collected data that examines different aspects of mumps immunity and are limited in their predictive value for future outbreaks ( 253 ).…”

Measles, mumps, rubella prevention: how can we do better?

“…A previous study has shown that although neutralizing antibody titers were lower against some mumps virus strains than others, genetically diverse strains were neutralized in the sera obtained from children 6 weeks after the MMR vaccine administration [155]. Other studies conducted during mumps outbreaks have shown that the currently used genotype A vaccines provide suboptimal protection against genotype G, even if MMR vaccination was associated with less severe disease [37], and induce significantly lower neutralization titers against wild-type genotypes than against the vaccine strain [177,182]. Moreover, molecular evidence suggested that emergent mumps virus strains have different antigenic epitopes than vaccine strains [183].…”

“…In many parts of the world, outbreaks have been attributed to different genotype variants (genotypes I, J, F, G, C, H, K) as compared to the vaccine strains [26,37,107,155,[171][172][173][174][175][176][177][178][179][180][181]. In particular, recent outbreaks of mumps caused by the genotype G virus have been reported in several countries, such as the USA, Canada, Norway, Scotland, and Belgium [37,155,[177][178][179][180][181]. While differences between vaccine and circulating strains may induce vaccine escape and favor outbreaks, the major cause of mumps outbreaks seems to be the waning immunity after vaccination and contradicting literature exists as to the importance of the mumps genetic variants [107,155].…”