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Randomized Controlled Trial
. 2023 May;4(5):e300-e308.
doi: 10.1016/S2666-5247(22)00332-9. Epub 2023 Apr 17.

Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial

Anna Calvert  1 , Gayatri Amirthalingam  2 , Nick Andrews  2 , Sneha Basude  3 , Matthew Coleman  4 , Hannah Cuthbertson  5 , Anna England  5 , Vanessa Greening  6 , Bassam Hallis  5 , Edward Johnstone  7 , Christine E Jones  8 , Konstantinos Karampatsas  6 , Asma Khalil  6 , Kirsty Le Doare  9 , Mary Matheson  5 , Elisabeth Peregrine  10 , Matthew D Snape  11 , Manu Vatish  12 , Paul T Heath  6 ; OpTIMUM Study Group
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Free article
Randomized Controlled Trial

Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial

Anna Calvert et al. Lancet Microbe. 2023 May.
Free article

Abstract

Background: Pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation. In this trial we aimed to investigate the equivalence of three time periods for pertussis vaccination in pregnancy.

Methods: In this open-label, equivalence, randomised controlled trial to investigate equivalence of different time windows for pertussis vaccination in pregnancy, participants were randomly assigned (1:1:1 ratio) to receive a pertussis-containing vaccine (Boostrix-inactivated poliovirus vaccine) in one of three gestational age groups, comprising group 1 (≤23 weeks + 6 days), group 2 (24-27 weeks + 6 days), and group 3 (28-31 weeks + 6 days) using a computer-generated randomisation list. The primary outcome was concentration of pertussis-specific antibodies in the infant born at term at birth. Maternal blood sampling was done before and 2 weeks after vaccination and at delivery, together with a cord sample, and an infant sample was collected at least 4 weeks after primary vaccination. Reactogenicity was assessed for 7 days after vaccination. This trial was registered with ClinicalTrials.gov (NCT03908164).

Findings: Between May 7, 2019, and Feb 13, 2020, of 1010 women assessed for eligibility, 364 women were recruited and 351 received the intervention (120 in group 1, 119 in group 2, and 112 in group 3). Equivalence of time periods was demonstrated for anti-pertussis toxin and anti-pertactin IgG concentrations. The cord blood geometric mean concentrations of anti-filamentous haemagglutinin IgG were higher with increasing gestational age at vaccination, such that for infants in group 1 (≤23 weeks + 6 days), equivalence to group 3 (28-31 weeks + 6 days) was not shown. Reported rates of fever were similar between study groups.

Interpretation: Pertussis vaccination at three different time intervals in pregnancy resulted in equivalent concentrations of IgG antibodies in infants against two of the three pertussis antigens assessed. Overall, these findings support recommendations to vaccinate any time between 16 weeks and 32 weeks of gestation.

Funding: The Thrasher Research Fund and the National Immunisation Schedule Evaluation Consortium through the National Institute for Health and Care Research policy research programme.

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Conflict of interest statement

Declaration of interests GA and NA report that the Immunisation and Vaccine Preventable Diseases Division has provided vaccine manufacturers with postmarketing surveillance reports on pneumococcal and meningococcal infection, which the companies are required to submit to the UK Licensing Authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. CEJ has done studies on behalf of the University of Southampton and University Hospital Southampton NHS Foundation Trust funded by vaccine manufacturers, including Novavax, Moderna, Medicago, and Pfizer, but receives no personal funding for these activities. CEJ has served on advisory boards, data safety monitoring boards, or as a consultant for Moderna, MSD, Sanofi, Minervax, and Pfizer. MDS has acted as an investigator on behalf of the University of Oxford for studies funded or supported by vaccine manufacturers including GlaxoSmithKline, Pfizer, MCM vaccines, Novavax, AstraZeneca, and Janssen. MDS received no direct financial benefit for this work. From September, 2022 (after completion of this work), MDS became an employee of Medimmune and Moderna. PTH has conducted studies on behalf of St George's, University of London funded by vaccine manufacturers, including AstraZeneca, Novavax, Moderna, Valneva, Janssen, Minervax, and Pfizer, but receives no personal funding for these activities. All other authors declare no competing interests.

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