Measles and mumps, two related viruses with distinct challenges for global vaccination programs, Prof. Annette Mankertz

Measles and mumps, two related viruses with distinct challenges for global vaccination

programs

Annette MankertzFG12, NRZ MMR, RRL WHO EUR

13.11.2015, ESCAIDE StockholmEmerging challenges to vaccine programmes:

antigen escape and non-specific immune effects

http://ecdc.europa.eu/en/healthtopics/measles/PublishingImages/ECDC_measles_infographics2014_contagious.pdf

MM(R) vaccine • Measles vaccine by John F. Enders • 1954, throat swab of David

Edmonston• Cultivation/attenuation in cell

culture/animals• Tests in Africa and U.S., FDA

license in 1963

• Mumps vaccine by Maurice Hillemanns

• 1963, throat swab of Jeryl Lynn• Cultivation/attenuation in cell

culture

Molecular Epidemiologyperformed by NRC MMR

• Sample collection tools can be ordered online

• German GP, Ped, LHA, clinics send samples of suspected MMR cases

• Questionnaire provides additional data (date of sampling and vaccination, symptoms, travelling history…)

• Diagnostics (serology, PCR)• molecular surveillance

Is the vaccine still protective?• > 60 years old• Co-circulation with wt-virus, loss of neutralizing epitopes

recognized by vaccine induced antibodies?• Measles-incidence declining, loss of natural booster?

• 1000 submissions to NRC analysed with respect to vaccination status – Primary vaccination failure (PVF): no vaccination reaction;

vaccine still effective?– Secundary vaccination failure (SVF): waning titers; sufficient

long-term immunity?

Sekundary vaccination failure are infrequently detected - (but it can be infectious)

• Index Patient with 2 doses MMR (3 and 4 y)• Female patient (22), New York, box office• Fell ill, 88 contacts over several days• 4 (3 HCW, 1 colleague) contracted measles (all 1. d; 2xMMR or IgG pos) • clinical symptoms, lab-confirmed• typical secondary immune-answer : PCR pos, high-avidity IgG, high PNT titer

• 6/2011: 3 Ketten von ‘D8-Villupuram’ nach

Massenereignis in Rimini, Italien

• Deutschland: 13 primäre Infektionen, Alter 11 -27

• Slovenien: 15 Fälle, 28 -47, 9 Fälle sekundäres

Impfversagen

• Unterschiedliche Suszeptible

– ungeschützte Jugendliche in Deutschland

– Geimpfte mittleren Alters in Slowenien (nach 30 Jahren

ohne Masern)

Euro Surv, Sept. 2014

8

Conclusions

• The measles and mumps vaccine have been in use for > 60 years

• Measles:• Neutralizing epitopes of H protein undergo changes• Efficacy of the measles vaccine is high• SVF are observed. Frequency of SVF is related to epidemiologic

situation• MV elimination should be accelerated, because the efficiency

of the vaccine cannot be taken for granted

Mumps outbreaks affecting the vaccinated reported Europe and elsewhere

Genotype G (5)

Has genotype G caused a vaccine break-through? Is the MMR vaccine still efficient?

IgM pos

IgG pos n = 8 (vacc = 3)

IgM neg/equ

IgG pos n = 29 (vacc = 20)

IgM neg

IgG neg n = 2 (vacc = 1)

serum n.a.

n = 6 (vacc = 1)

PCR posn = 45

genotype G n = 37/37 PCR n.a.

IgM pos/IgG pos

n = 2 (vacc=1)

PCR neg

IgM pos/IgG posn = 4 (vacc=1)

Laboratory investigation of 145 suspected mumps cases in 2011

IgM- and/or PCR-positive cases

N = 51/145 (vaccinated*: 1 dose = 27, 2 doses = 16)

* MuV-containing vaccine given several years before the onset of clinical signs

cultivation n = 10/14

Diagnosing mumps (in vaccinated)• 2008 - 2013, samples from 534 suspected mumps cases

submitted to NRC• 216 cases (40%) pos (PCR and/or serology)• 65% affected 15 to 29 y (median 26.4 y) • 69%* had a history of prior vaccination• PCR detected cases during the first week (74% pos) • PCR worked best in throat swabs and oral fluids (61% pos) • IgM was more reliable in the second week (67%), but not in

vaccinated mumps cases (30%)

• * of those with vaccination data available

Possible constellation of serologic results IgG (ELISA) bind to antigen /

neutr. antibodies (FRNT) inhibit infection

naive protected Vaccine break-through

IgG

neutr.Ab wt

neutr.Ab vaccine

Cut off IgG

Cut off neutr. assay

Credits• Ingrid Deitemeier• Christine Schwerdtfeger• Petra Kurzendörfer• Anne Wolbert• Martin Körbs• Heidrun Ranisch

• Dr. Sabine Santibanez• Dr. Christina Poethko-Müller• Dr. Dorothea Matysiak-Klose

• Colleagues in local health agencies• Pediatricians and clinicians