Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic

Abstract

In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases, young adults were affected who have acquired immunity against mumps solely by vaccination and not by previous wild-type mumps virus infection. To investigate mumps-specific antibody levels, functionality and dynamics during a mumps epidemic, blood samples were obtained longitudinally from 23 clinical mumps cases, with or without a prior history of vaccination, and from 20 healthy persons with no serological evidence of recent mumps virus infection. Blood samples from mumps cases were taken 1–2 months and 7–10 months after onset of disease. Both vaccinated and unvaccinated mumps cases had significantly higher geomean concentrations of mumps-specific IgG (resp. 13,617 RU/ml (95% CI of 9,574–19,367 RU/ml) vs. 1,552 (445–5412) RU/ml at 1–2 months; and 6,514 (5,247–8,088) RU/ml vs. 1,143 (480–2,725) RU/ml at 7–10 months) than healthy controls (169 (135–210) RU/ml) (p = 0.001). Patterns in virus-neutralizing (VN) antibody responses against the mumps vaccine virus were similar, vaccinated and unvaccinated mumps cases had significantly higher ND₅₀ values at both time points of sampling (resp 4,695 (3,779–5,832) RU/ml vs. 1,533 (832–2,825) RU/ml at 1–2 months; 2,478 (1,968–3,122) RU/ml vs. 1,221 (1,029–1,449) RU/ml at 7–10 months) compared with (previously vaccinated) healthy controls (122 (196–76)) RU/ml) (p = 0.001) The unvaccinated mumps cases had significantly lower mumps-specific IgG and VN antibody concentrations at both sampling points compared with previously vaccinated cases, but their antibody concentrations did not differ significantly at the 2 time points. In contrast, the mumps-specific IgG and VN antibody concentrations of the previously vaccinated mumps cases were significantly higher within the first 2 months after onset of mumps and declined thereafter, characteristic for a secondary response. A moderate correlation was found between the level of mumps-specific IgG serum antibodies and VN antibodies for the mumps cases (r = 0.64; p<0.001).

Keywords:

• antibody response
• antibody dynamics
• epidemic
• mumps
• vaccination
• virus neutralization

Abbreviations:

• MMR, measles mumps and rubella
• ND₅₀, reciprocal virus-neutralizing antibody dose
• VN, virus-neutralizing antibody
• RU/ml, RIVM units per ml
• GMC, geometric mean concentration
• 95% CI, lower and upper 95% confidence intervals of GMC

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors are grateful to Lidian Izeboud (Julius Center for Health Sciences and Primary Care at the UMC, Utrecht, the Netherlands) and Anneke Westerhof (RIVM) who performed the study visits, including venous blood sampling, and Nynke Rots, Marianne van der Sande and Susan Hahné for respectively supervision and coordination of the clinical study. Furthermore, we would like to thank the Municipal Health Services, Tessa Schurink-van‘t Klooster and Olga Ophorst for participant recruitment, Martien Poelen and Kina Helm for blood sample handling, Gaby Smits for providing instructions for the multiplex IgG immunoassay (MIA), and Mirjam Knol for assistance with statistical analysis. Finally, we would like to express our gratitude to all participants.

Funding

The study was funded by ZonMw and the Dutch Ministry of Health, Welfare and Sport (VWS).