Lessons learned from non-RSV maternal immunization; safety, immunogenicity and effectiveness

Hester de Melker

Nicoline vd Maas

Cib – RIVM

Epidemiology and Surveillance Unit; NIP department

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Department NIP – Epidemiology and Surveillance Center of Infectious Disease Control, RIVM

maternal vaccination; lessons learned

Introduction of HPV-vaccination

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maternal vaccination; lessons learned

Public health and regulators have similar scope

● Vaccination status of possible Adverse Events Following Immunisation

→ causal of coïncidental relation?

● Valid information about vaccination status

→ ‘vaccine failure’ of ‘failure to vaccinate’?

Monitoring is important

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maternal vaccination; lessons learned

Content: maternal vaccination

● Principles

● Longer term experience

› Tetanus

● More recent experience

› Pandemic influenza

› Pertussis

● Lessons learned

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maternal vaccination; lessons learned

Principles of maternal vaccination

● Transplacental transport of IgG Malek A, et al. American journal of reproductive immunology.1996;36(5):248-55.

– Start from 13w-17w pregnancy duration

– Mainly in the last 4 wks of pregnancy

– Various IgG classes transported with different efficacy

– Infection in the mother can negatively influence the transport

● Sometimes active transport; concentrations in child can be higher than in the mother

● Gives passive immunisation in the newborn

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maternal vaccination; lessons learned

Possible disadvantages of maternal vaccination

● Blunting = maternal antibodies decrease the immune response after vaccination in the child

● Safety for mother and child

– Contraindication for live attenuated vaccines

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maternal vaccination; lessons learned

Maternal tetanus vaccination to prevent maternal and neonatal tetanus

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maternal vaccination; lessons learned

tetanus

Neonatal tetanus: a preventable disease

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maternal vaccination; lessons learned

Neonatal tetanus in New Guinea; Schofield, BMJ, 1961

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maternal vaccination; lessons learned

Elimination of maternal and neonatal tetanus

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maternal vaccination; lessons learned

Maternal H1N1-vaccination

● Spring 2009 an influenza A (H1N1) pandemic

● Increased risk on hospitalisations due to respiratory complications, in particular for women with co-morbidity

● During 2009 pandemic, an increased risk of adverse pregnancy outcomes after infection

● Limited data on safety of vaccination during pregnancy

› FDA, CDC, EMA, ECDC -> strenghtening surveillance studies

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maternal vaccination; lessons learned

Maternal H1N1-vaccination and risk on foetal death

Haberg SE,et al. N Engl J Med. 2013;368(4):333-40.

Safety and maternal H1N1-vaccination ● Pasternak B, et al. Vaccination against pandemic A/H1N1 2009 influenza in pregnancy and risk of fetal

death: cohort study in Denmark. BMJ. 2012;344:e2794.

● Pasternak B, et al. Risk of adverse fetal outcomes following administration of a pandemic influenza A(H1N1) vaccine during pregnancy. JAMA. 2012;308(2):165-74.

● Chavant F, et al. The PREGVAXGRIP study: a cohort study to assess foetal and neonatal consequences of in utero exposure to vaccination against A(H1N1)v2009 influenza. Drug Saf. 2013;36(6):455-65.

● Heikkinen T, et al. Safety of MF59-adjuvanted A/H1N1 influenza vaccine in pregnancy: a comparative cohort study. Am J Obstet Gynecol. 2012;207(3):177 e1-8.

● Kallen B, et al. Vaccination against H1N1 influenza with Pandemrix((R)) during pregnancy and delivery outcome: a Swedish register study. BJOG. 2012.

● Launay O, et al. Low rate of pandemic A/H1N1 2009 influenza infection and lack of severe complication of vaccination in pregnant women: a prospective cohort study. PLoS One. 2012;7(12):e52303.

● Ludvigsson JF, et al. Influenza H1N1 vaccination and adverse pregnancy outcome. European journal of epidemiology. 2013;28(7):579-88.

● Nordin JD, et al. Maternal influenza vaccine and risks for preterm or small for gestational age birth. J Pediatr. 2014;164(5):1051-7 e2.

● Richards JL, et al. Neonatal outcomes after antenatal influenza immunization during the 2009 H1N1 influenza pandemic: impact on preterm birth, birth weight, and small for gestational age birth. Clin Infect Dis. 2013;56(9):1216-22.

● Sammon CJ, Snowball J, McGrogan A, de Vries CS. Evaluating the hazard of foetal death following H1N1 influenza vaccination; a population based cohort study in the UK GPRD. PLoS One. 2012;7(12):e51734.

● Steinhoff MC, et al. Neonatal outcomes after influenza immunization during pregnancy: a randomized controlled trial. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2012;184(6):645-53.

● Trotta F, et al. Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study. BMJ. 2014;348:g3361.

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Safety and maternal H1N1-vaccination in the Netherlands

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maternal vaccination; lessons learned

Logistic regression analysis of H1N1 vaccination

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Vacci nated

SGA Pre term

Composite outcome

Yes 528 Ref Ref Ref

No 1123 0.84 0.50-1.43 0.98 0.59-1.62 0.86 0.46–1.64

Composite adverse outcome: Apgar score

Pertussis

● Pertussis containing vaccines have been used in routine vaccination programmes since 1950s

● Programmes has led to reduction in pertussis disease with vaccination starting in general at 2 to 3 months of age

● Still pertussis is endemic, with epidemic peaks

● Most severe disease among infants too young to be vaccinated

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maternal vaccination; lessons learned

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0

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2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

1-4 jaar 5-9 jaar 10-19 jaar 20-59 jaar 6-11 mnd 0-5 mnd

Incidence of pertussis in The Netherlands

Reconciled deaths from pertussis in infants (England only)

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2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Maternal pertussis vaccination ● Recommended in VS, UK, Belgium,

Australia, Israel, Spain

● Vaccination uptake in UK and

Belgium ≈ 60%

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maternal vaccination; lessons learned

Monitoring maternal pertussis vaccination

● Safety

● Effectiveness

› Prevention of severe pertussis in young infants

● Immunogenicity

› Response in infants

› Timing of vaccination in pregnancy

› Optimizing vaccination schedule in infants

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maternal vaccination; lessons learned

Transplacental IgG transport

Abu Raya B, et al. Vaccine. 2014;32(44):5787-93.

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maternal vaccination; lessons learned

Effectiveness maternal pertussis vaccination UK

Amirthalingham et al. Lancet 2014

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maternal vaccination; lessons learned

Dabrera et al. Clin Infect Dis 2015

Effectiveness maternal vaccination UK

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maternal vaccination; lessons learned

• No increased risk of stillbirth, maternal or neonatal death, (pre-) eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or child renal failure. Donegan et al., BMJ, 2014. Kharbanda et al., JAMA, 2014

• No adverse events or systemic symptoms. Munoz et al., JAMA 2014

• Increased incidence of chorioamnionitis (RR 1,19; 95%CI 1,13-1,26). Kharbanda et al., JAMA, 2014

• Study on 7378 women (7152 with maternal pertussis vaccination,

226 controls): preterm birth rates, small for gestational age and length of neonatal hospitalization durante partu similar. Morgan et al, American College of Obstetricians and Gynecologists, 2015

Safety of maternal pertussis vaccination

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maternal vaccination; lessons learned

Blunting after maternal pertussis vaccination

Hardy-Fairbanks AJ, et al. Pediatr Infect Dis J. 2013;32(11):1257-60.

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maternal vaccination; lessons learned

Maternal vaccination early in pregnancy maximizes antibody transfer – Eberhardt et al. 2016

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maternal vaccination; lessons learned

MIKI-study; RIVM

60 women per arm

Current NIP

- 2,3,4 and 11 mo

MIKI-schedule

- 3, 5, 11 mo

Study immunogenicity NIP-components up to preschool booster (4 years)

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maternal vaccination; lessons learned

Some lessons learned from non-RSV maternal vaccination

● Experience with safe and effective vaccines

– Tetanus, H1N1 influenza vaccination

● In recent years various countries have succesfully introduced maternal pertussis vaccination

● Monitoring safety, effectiveness and immunogenicity is essential

› Adverse Events Following Immunisation > Public trust

› Occurrence of disease in infants

– Vaccine failure vs ‘failure’ to vaccinate

› Optimize infants vaccination schedule

› Optimizing maternal vaccination schedule

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maternal vaccination; lessons learned

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maternal vaccination; lessons learned

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