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

1. Measles and mumps, two related
viruses with distinct challenges for
global vaccination programs
Annette Mankertz
FG12, NRZ MMR, RRL WHO EUR
13.11.2015, ESCAIDE Stockholm
Emerging challenges to vaccine programmes:
antigen escape and non-specific immune effects

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

3. 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

4. Molecular Epidemiology
performed 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

5. 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?

6. 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

7. • 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
8

9. Mumps outbreaks affecting the vaccinated
reported Europe and elsewhere
Has genotype G caused a vaccine break-through? Is the MMR vaccine still efficient?

10. 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 pos
n = 45
genotype G
n = 37/37
PCR n.a.
IgM pos/IgG pos
n = 2 (vacc=1)
PCR neg
IgM pos/IgG pos
n = 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

11. 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

12. 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

13. 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