Available online 21 September 2022, 105296

ABSTRACTBackground

Despite widespread use of the mumps vaccine resulting in significant reduction in the incidence of symptomatic mumps infection, large outbreaks continue to occur in highly vaccinated populations.

Objectives

We examined the mumps-specific IgG, IgG subclasses and neutralization titres to the outbreak Genotype G5 and Jeryl Lynn vaccine (Genotype A) mumps strains.

Study design

Sera from 207 individuals were classified into five distinct cohorts: healthy controls and mumps cases of 5-17 years and 18-25 years, and naturally infected individuals of 50+ years. Mumps specific IgG and IgG subclass levels were measured using modified ELISA assays with lysates and nucleoprotein antigens from both the mumps vaccine and circulating Genotype G5 strains. All sera were investigated for in vitro neutralizing antibody titres (GMT) using focus reduction neutralization assays. Data was analysed using the Kruskal-Wallis test and pairwise Wilcoxon tests.

Results

Mumps cases had higher mumps IgG levels compared to controls, to both the vaccine and outbreak strains, however levels decreased with age. Mumps IgG3 levels were significantly raised in mumps cases (p<0.001). Neutralization titres were lower to the outbreak strain in all cohorts with titres markedly lower in the mumps cohorts compared to healthy controls. Mean GMT to the vaccine strain increased with age. The naturally infected group displayed the highest GMT to the JL vaccine and the lowest GMT to the outbreak strain.

Conclusions

Antigenic differences between mumps vaccine strain and circulating mumps viruses decrease the cross-neutralization capacity of vaccine-induced antibodies which may play a role in breakthrough infection.

Section snippetsINTRODUCTION

Mumps is an enveloped, negative-sense, single stranded RNA paramyxovirus spread by respiratory droplets. Up to 30% of primary infections are asymptomatic or have mild non-specific symptoms [1]. In the remainder of patients more severe symptoms, commonly parotitis, and less frequently orchitis and encephalitis can occur [2, 3].

Prior to mumps vaccination, epidemic peaks of infection occurred every 2-5 years, with mumps remaining endemic in children [4, 5]. The mumps vaccine was first licensed in

Samples

The study population consisted of serum samples collected from the following 6 groups:

1

Healthy controls (HC) aged 5-17 years (young)

2

Healthy controls aged 18-25 years (old)

3

Mumps cases (M) aged 5-17 years

4

Mumps cases aged 18-25 years

5

Naturally infected individuals (N) aged 50+ years

6

Mumps-specific IgG negative individuals

Groups 1 and 2 reported receiving 2 MMR doses. Groups 3 and 4 were collected during the large mumps outbreak of 2018-2019 in Ireland and were clinically confirmed acute mumps cases

RESULTS

Two hundred and seven serum samples were analysed for mumps-specific IgG and IgG subclasses to both Jeryl Lynn (vaccine) and genotype G5 (outbreak) strains. Twelve individuals were LIAISON® mumps IgG negative (Group 6). The remaining 195 samples were mumps IgG positive and were divided into five distinct cohorts - ‘young’ (5-17 years of age), and ‘old’ (18-25 years of age), both with samples from mumps infected patients and healthy controls. Each group was up to 12 and 20 years (‘young’ and

DISCUSSION

Prior to the introduction of the mumps vaccine, epidemiological studies concluded that immunity following natural mumps infection is generally life-long, aided by natural boosting due to exposure to mumps virus in the community [19]. Following vaccination however, mumps immunity has been reported to persist for a mean duration of 27 years, but one-quarter of vaccinated persons may lose immunity within 8 years [20]. Waning of vaccination-induced immunity may be a contributory factor to

Funding

This research was funded by the National Children's Research Centre, Crumlin [Grant No. C/18/11] awarded to JH.

CRediT authorship contribution statement

Deirdre Jane Foley: Writing – original draft, Formal analysis, Visualization, Writing – review & editing. Anna Rose Connell: Investigation, Methodology, Writing – review & editing. Gabriel Gonzalez: Formal analysis, Visualization. Jeff Connell: Resources, Methodology, Writing – review & editing. Timothy Ronan Leahy: Resources, Writing – review & editing. Cillian De Gascun: Resources, Writing – review & editing. Jaythoon Hassan: Conceptualization, Methodology, Supervision, Project

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank all the individuals for providing samples, the staff of Virus Isolation, National Virus Reference Laboratory for supplying plates of FRhK4 cells, and Drs. Bridget Hogg, UCD School of Veterinary Medicine and Alejandro Garcia Abner, UCD Centre for Pathogen Host Research for providing laboratory space for some of the neutralization assays.

References (29)RE Weibel et al.Attenuated Mumps-Virus Vaccine III. Clinical and serologic aspects in a field evaluation

New England Journal of Medicine

(1967)

XX Gu et al.Waning Immunity and Microbial Vaccines-Workshop of the National Institute of Allergy and Infectious Diseases

Clin Vaccine Immunol

(2017)

Mumps outbreak in Ireland 2014-2015- a review. Vol. 16, Epi-Insight

Disease surveillance report of HPSC Ireland

(2015)

A Ferenczi et al.Ongoing mumps outbreak among adolescents and young adults, Ireland, August 2018 to January 2020

Eurosurveillance

(2020)

View full text

© 2022 Elsevier B.V. All rights reserved.