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. 2013 Jun;141(6):1298-309.
doi: 10.1017/S0950268812001896. Epub 2012 Sep 7.

Antigenic differences between vaccine and circulating wild-type mumps viruses decreases neutralization capacity of vaccine-induced antibodies

M Šantak  1 , M Lang-Balija, J Ivancic-Jelecki, T Košutić-Gulija, S Ljubin-Sternak, D Forcic
Affiliations

Antigenic differences between vaccine and circulating wild-type mumps viruses decreases neutralization capacity of vaccine-induced antibodies

M Šantak et al. Epidemiol Infect. 2013 Jun.

Abstract

A recent resurgence of mumps in doubly vaccinated cohorts has been observed, identifying genotype G as the current predominant genotype. In this study, the neutralization efficacy of guinea pig sera immunized with three vaccine viruses: L-Zagreb, Urabe AM9 and JL5, was tested against seven mumps viruses: three vaccine strains and four wild-type strains (two of genotype G, one of genotype C, one of genotype D) isolated during 1998-2011. All sera neutralized all viruses although at different levels. The neutralization efficiency of sera decreases several fold by temporal order of virus isolation. Therefore, we concluded that gradual evolution of mumps viruses, rather than belonging to a certain genotype, results in an antigenic divergence from the vaccine strains that decrease the neutralization capacity of vaccine-induced antibodies. Moreover, the amino-acid sequence alignment revealed three new potentially relevant regions for escape from neutralization, i.e. 113-130, 375-403 and 440-443.

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Figures

Fig. 1.
Fig. 1.
The number of publications on mumps outbreaks or associated vaccine failure studies during 2000–2011.
Fig. 2.
Fig. 2.
Phylogenetic tree based on the entire SH gene presenting currently assigned reference strains (genotypes are indicated by the capital letters in square brackets; uncl, unclassified strains) [1], three vaccine strains (L-Zagreb, Urabe AM9, JL5), representative strains of genotype G (including strains Du/CRO05 and MuVi/Split.CRO/05.11) and two wild-type viruses of non-genotype G (9218/Zg98 and Zg/CRO05).
Fig. 3.
Fig. 3.
Serum levels of mumps virus antibodies in guinea pig sera immunized with either (a) L-Zagreb, (b) Urabe AM9, or (c) JL5 measured by haemagglutination inhibition (HI) test. •, Represents the titre value of a single serum; ◊, represents the average value of all sera.
Fig. 4.
Fig. 4.
Serum levels of mumps virus antibodies in guinea pig sera immunized with either (a) L-Zagreb, (b) Urabe AM9, or (c) JL5 measured by plaque-reduction neutralization test (PRNT). •, Represents the titre value of a single serum; ◊, represents the average value of all sera.
Fig. 5.
Fig. 5.
Phylogenetic tree based on the complete HN protein sequence presenting three vaccine strains (L-Zagreb, Urabe AM9, JL5) and several wild-type strains during 1998–2011.
Fig. 6.
Fig. 6.
Pairwise sequence alignment of the previously identified (a) epitopes and (b) regions suggested in this study to be involved in the viral escape from neutralization antibodies for the HN protein of the three mumps virus vaccine strains (L-Zagreb, Urabe AM9, JL5) and several wild-type mumps virus strains. Genotypes are indicated by capital letters in parentheses. Amino acids differing from the L-Zagreb strain are indicated by single-letter codes.
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