Identification of naturally processed #mumps virus epitopes by mass spectrometry: Confirmation of multiple CD8+ T cell responses in mumps patients (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Identification of naturally processed mumps virus epitopes by mass spectrometry: Confirmation of multiple CD8+ T cell responses in mumps patients

Jelle de Wit, Maarten E Emmelot, Hugo Meiring, Jacqueline A M van Gaans-van den Brink, Cécile A C M van Els, Patricia Kaaijk

The Journal of Infectious Diseases, jiz480, https://doi.org/10.1093/infdis/jiz480

Published: 27 September 2019

 

Abstract

Background

The re-emergence of mumps among vaccinated young adults has become a global issue. Besides waning of antibody responses, suboptimal induction of T cell responses may reduce protection. Recently, we observed a dominant polyfunctional CD8+ T cell response after natural mumps virus (MuV) infection that was not present after vaccination. Unraveling the MuV epitope-repertoire can provide insight in the specificity, functionality, and breadth of the T cell response against MuV.

Methods

Peptides were eluted from HLA class I molecules of MuV-infected cells and characterized by advanced mass spectrometry. Selected identified MuV peptides were tested for in vitro and ex vivo immunogenicity.

Results

Here we identified a broad landscape of 83 CD8+ T cell epitopes of MuV, of which 41 were confirmed based on synthetic peptide standards. For six epitopes we showed induction of an HLA-A*02-restriced CD8+ T cell response. Moreover, robust T cell responses against five selected MuV epitopes could be detected in all tested mumps patients using peptide/HLA-A*02:01 dextramers.

Conclusion

The identified CD8+ T cell epitopes will help to further characterize MuV-specific T cell immunity following natural MuV infection or vaccination. These MuV epitopes may provide clues for a better understanding of, and possibly for preventing, mumps vaccine failure.

MMR, immunopeptidome, T cell immunity, mumps infection, MHC class I

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: Mumps; Vaccines.

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Decreased #humoral #immunity to #mumps in young #adults immunized with #MMR #vaccine in #childhood (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood

Mohammed Ata Ur Rasheed, Carole J. Hickman, Marcia McGrew, Sun Bae Sowers, Sara Mercader, Amy Hopkins, Vickie Grimes, Tianwei Yu, Jens Wrammert, Mark J. Mulligan, William J. Bellini, Paul A. Rota, Walter A. Orenstein, Rafi Ahmed, and Srilatha Edupuganti

PNAS first published September 3, 2019 / DOI: https://doi.org/10.1073/pnas.1905570116

Contributed by Rafi Ahmed, July 18, 2019 (sent for review April 2, 2019; reviewed by Rino Rappuoli and Robert Seder)

 

Significance

The live-attenuated mumps-measles-rubella (MMR) vaccine has been highly successful in the United States since its introduction 47 years ago. However, for the past decade, mumps outbreaks have been occurring among young adults who were vaccinated as children. Waning immunity has been proposed as a key contributing factor to mumps resurgence. In our sample (n = 71) of 18- to 23-year-old college students, the majority had detectable mumps IgG antibodies by enzyme-linked immunosorbent assay (ELISA) but the magnitude was lower than rubella. Neutralizing antibody titers were 6-fold lower to a circulating genotype G mumps strain versus the vaccine strain. Ten percent of our participants had no detectable memory B cells to mumps. Strategies are needed to improve immunity to the mumps vaccine.

 

Abstract

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

mumps, measles, rubella – MMR vaccine – memory B cells (MBCs) – plaque reduction  -neutralization titers – IgG ELISA

 

Footnotes

1 To whom correspondence may be addressed. Email: rahmed@emory.edu or sedupug@emory.edu.

Author contributions: M.A.U.R., C.J.H., W.J.B., W.A.O., R.A., J.W., and S.E. designed research; M.A.U.R., C.J.H., M.M., S.B.S., S.M., A.H., V.G., and S.E. performed research; M.A.U.R., C.J.H., S.B.S., S.M., T.Y., and S.E. analyzed data; and M.A.U.R., C.J.H., J.W., M.J.M., W.J.B., P.A.R., W.A.O., R.A., and S.E. wrote the paper.

Reviewers: R.R., GlaxoSmithKline; and R.S., NIH.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1905570116/-/DCSupplemental.

Published under the PNAS license.

Keywords: Mumps; Vaccines; Serology; Seroprevalence; Immunoglobulins.

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A third dose of #MMR #vaccine to improve #immunity against #mumps in young #adults (J Infect Dis., abstract)

[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

A third dose of measles-mumps-rubella vaccine to improve immunity against mumps in young adults

Patricia Kaaijk, Alienke J Wijmenga-Monsuur, Marlies A van Houten, Irene K Veldhuijzen, Hinke I ten Hulscher, Jeroen Kerkhof, Fiona R van der Klis, Rob S van Binnendijk

The Journal of Infectious Diseases, jiz188, https://doi.org/10.1093/infdis/jiz188

Published: 23 April 2019

 

Abstract

Background

Waning of vaccine-induced immunity is considered to play a central role in the re-emergence of mumps among vaccinated young adults. The aim of the present study was to investigate antibody responses and safety of a third dose of measles-mumps-rubella vaccine (MMR-3) in 150 young adults. Antibody levels were related to a surrogate of protection based on pre-outbreak serum antibody levels of persons with (n=31) or without serological evidence of mumps (n=715).

Methods

IgG and virus-neutralizing (FRNT) antibody responses against both the mumps Jeryl Lynn (JL) vaccine and the G outbreak strain were determined, and vaccine safety was evaluated.

Results

Four weeks following MMR-3 receipt, antibody levels increased by a factor 1.65, 1.34 and 1.35 for IgG, JL/FRNT, and G/FRNT, respectively. Despite an antibody decline one year later, levels were still above baseline (factor 1.37, 1.15, 1.27). Based on the surrogate protective antibody cutoff level, significantly more participants were protected against mumps virus infection up to one year after vaccination, i.e. above the presumed threshold for herd immunity.

Conclusions

MMR-3 vaccination increased antibody levels that may protect against mumps infection for longer than previously assumed, and is expected to be a good and safe intervention for controlling a mumps outbreak.

Clinical Trials Registration 2016-001104-36 (EudraCT); NTR5911

mumps, measles-mumps-rubella (MMR) vaccine, immunogenicity, antibody response, safety

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: Mumps; Vaccines.

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#Mumps in a highly vaccinated Marshallese community in #Arkansas, #USA: an #outbreak report (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Mumps in a highly vaccinated Marshallese community in Arkansas, USA: an outbreak report

Virgie S Fields, MS, Haytham Safi, MD, Catherine Waters, RN, Jennifer Dillaha, MD, Lucy Capelle, Prof Sheldon Riklon, MD, Prof J Gary Wheeler, MD, Dirk T Haselow, MD

Published: January 08, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30607-8

 

Summary

Background

During 2000–15, Arkansas Department of Health, Little Rock, AR, USA, investigated between one and six cases of mumps each year. From Aug 5, 2016, to Aug 5, 2017, the department received notification of more than 4000 suspected mumps cases in the second largest outbreak in the USA in the past 30 years.

Methods

Arkansas Department of Health investigated all reported cases of mumps to ascertain exposure, travel, and vaccination histories and identify close contacts. Cases were classified as confirmed if the patient had laboratory confirmation of mumps virus or probable if they had clinical symptoms and either a positive serological test or a known epidemiological link to a confirmed case.

Findings

2954 cases of mumps related to the outbreak were identified during the outbreak period: 1665 (56%) were laboratory confirmed, 1676 (57%) were in children aged 5–17 years, and 1692 (57%) were in Marshallese people. Among the 1676 school-aged cases, 1536 (92%) had previously received at least two doses of a vaccine containing the mumps virus. Although 19 cases of orchitis were reported, severe complications were not identified. Unusual occurrences, such as recurrent parotitis and prolonged viral shedding, were observed mostly in Marshallese individuals. Viral samples were characterised as genotype G.

Interpretation

This large-scale outbreak, primarily affecting a marginalised community with intense household crowding, highlights the need for coordinated, interdisciplinary, and non-traditional outbreak responses. This outbreak raises questions about mumps vaccine effectiveness and potential waning immunity.

Funding

Council of State and Territorial Epidemiologists and US Centers for Disease Control and Prevention.

Keywords: Mumps; USA; Arkansas; Vaccines.

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Ongoing #mumps #outbreak in #Israel, January to August 2017 (@eurosurveillanc, abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Eurosurveillance, Volume 22, Issue 35, 31 August 2017 / Rapid communication

Ongoing mumps outbreak in Israel, January to August 2017

V Indenbaum 1 2 , JM Hübschen 2 3 , C Stein-Zamir 4 , E Mendelson 1 , D Sofer 1 , M Hindiyeh 1 , E Anis 5 , N Abramson 4 , EJ Haas 5 , Y Yosef 6 , L Dukhan 6 , SR Singer 5

Author affiliations: 1. National Center for Measles/Mumps/Rubella, Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Tel Hashomer, Israel; 2. These authors contributed equally to this article and share first authorship; 3. Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; 4. Jerusalem District Health Office, Ministry of Health, Jerusalem, Israel; 5. Division of Epidemiology, Ministry of Health, Jerusalem, Israel; 6. Southern District Health Office, Ministry of Health, Beersheba, Israel

Correspondence: Judith M Hübschen ( Judith.Huebschen@lih.lu)

Citation style for this article: Indenbaum V, Hübschen JM, Stein-Zamir C, Mendelson E, Sofer D, Hindiyeh M, Anis E, Abramson N, Haas EJ, Yosef Y, Dukhan L, Singer SR. Ongoing mumps outbreak in Israel, January to August 2017. Euro Surveill. 2017;22(35):pii=30605. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.35.30605

Received:23 August 2017; Accepted:31 August 2017

 

Abstract

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected.

Keywords: Mumps; Israel.

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#Crossreactive and cross-neutralizing #activity of #human #mumps #antibodies against a novel mumps virus from #bats (J Infect Dis., abstract)

[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Cross-reactive and cross-neutralizing activity of human mumps antibodies against a novel mumps virus from bats

Shannon M. Beaty1, Raffael Nachbagauer1, Ariana Hirsh1, Frederic Vigant1, James Duehr1, Kristopher Azarm1, Alice J. Stelfox2, Thomas A. Bowden2, W. Paul Duprex3, Florian Krammer1 and Benhur Lee1

Author Affiliations: 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States; 2 Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; 3 Department of Microbiology, Boston University School of Medicine, Boston, United States

Corresponding author contact information. Correspondence and requests should be addressed to Dr. Benhur Lee, M.D. Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, #1124, New York, NY 10029. Telephone: 212-241-2552. Email address: benhur.lee@mssm.edu.

 

Abstract

To evaluate the antigenic relationship between bat mumps virus (BMV) and the JL5 vaccine strain of mumps virus (MuVJL5), we rescued a chimeric virus bearing the F and HN glycoproteins of BMV in the genomic background of MuVJL5. Cross-reactivity and cross-neutralization between this chimeric rMuVJL5-F/HNBMV virus and rMuVJL5 were demonstrated using hyperimmune mouse sera and a curated panel of human sera. All mouse and human sera that were able to neutralize rMuVJL5 infection had cross-neutralizing activity against rMuVJL5-F/HNBMV. Our data suggests that people who have neutralizing antibodies against MuV might be protected from infection by BMV.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Keywords: Mumps; Human; Bats.

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Estimating true #hospital #morbidity of #complications associated with #mumps #outbreak, #England, 2004/05 (@eurosurveillanc, abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Eurosurveillance, Volume 21, Issue 33, 18 August 2016 / Research article

Estimating true hospital morbidity of complications associated with mumps outbreak, England, 2004/05

C Yung 1 2 , M Ramsay 2

Author affiliations: 1. Infectious Disease Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore; 2. Immunisation, Hepatitis and Blood Safety Department, Public Health England, London, United Kingdom

Correspondence: Chee Fu Yung (cheefu.yung@gmail.com)

Citation style for this article: Yung C, Ramsay M. Estimating true hospital morbidity of complications associated with mumps outbreak, England, 2004/05 . Euro Surveill. 2016;21(33):pii=30320. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.33.30320

Received:21 July 2015; Accepted:03 June 2016

 

Abstract

Mumps outbreaks in highly vaccinated populations continue to be reported globally. Therefore, quantifying the burden of mumps morbidity accurately will be necessary to better assess the impact of mumps vaccination programmes. We aim to estimate the true morbidity resulting from mumps complications in terms of hospitalised orchitis, meningitis, oophoritis and pancreatitis in England during the outbreak in 2004/05. This outbreak in England led to a clear increase in hospitalisations coded to mumps for complications of orchitis in those born in the 1970s and 1980s and possibly for meningitis in those born in the 1980s. A simple statistical model, based on analysing time trends for diagnosed complications in hospital databases with routine laboratory surveillance data, found that the actual morbidity was much higher. There were 2.5 times (166 cases) more mumps orchitis cases in the 1970s cohort and 2.0 times (708 cases) more mumps orchitis cases in the 1980s cohort than complications coded to mumps in hospital databases. Our study demonstrated that the mumps outbreak in England 2004/05 resulted in a substantial increase in hospitalised mumps complications, and the model we used can improve the ascertainment of morbidity from a mumps outbreak.

Keywords: Research; Abstracts; Mumps; England.

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