Abstract

BACKGROUND: Immunisation in pregnancy against pertussis can reduce severe disease in infancy. There are few data on the safety and immunogenicity of vaccines given to pregnant women living with HIV and their infants. We aimed to describe the safety and immunogenicity of a tetanus-diphtheria-acellular pertussis (TdaP) vaccine containing genetically detoxified pertussis toxin given to pregnant women living with HIV and the effect of the vaccine on infant whole-cell pertussis vaccine responses. METHODS: We conducted an observer-blind, randomised, phase 2, multicentre, non-inferiority trial evaluating safety and immunogenicity of a vaccine containing genetically detoxified acellular pertussis in pregnant women living with HIV in Uganda. Women aged at least 18 years between 16 weeks and 26 weeks of gestation were randomly assigned to receive the tetanus-diphtheria (Td) vaccine or TdaP vaccine. Stratified block randomisation using blocks of four with a 1:1:1:1 ratio stratified by participant HIV status was used to distribute participants into equal groups (50 participants per group for a total of 200 participants). The intervention was a 0·5 mL single intramuscular dose of TdaP vaccine. Td or TdaP vaccination was randomly assigned to different clinic days using randomisation software. Primary immunogenicity endpoints were anti-pertussis toxin and anti-filamentous haemagglutinin IgG concentrations in infants at delivery and 18 weeks following three doses of a whole-cell pertussis containing vaccine. This study is registered at ClinicalTrials.gov, NCT04589312. FINDINGS: Between Oct 28, 2020, and May 21, 2021, 438 pregnant women were screened and 181 were randomly assigned: 90 to TdaP vaccine (40 HIV-positive participants and 50 HIV-negative participants) and 91 to Td vaccine (41 HIV-positive participants and 50 HIV-negative participants). All participants received Td, and 4 weeks later, 177 received either Td or TdaP. 32 serious adverse events occurred, none related to the study vaccine. At delivery, anti-pertussis toxin IgG concentrations for TdaP versus Td were superior in infants who were HIV-exposed but uninfected (geometric mean ratio 9·61, 95% CI 5·21-17·74) and HIV-unexposed infants (21·6, 11·2-41·7). In infants at 18 weeks, anti-pertussis toxin IgG concentrations for TdaP versus Td-vaccinated mothers were significantly lower for both infants who were HIV-exposed but uninfected (0·19, 0·09-0·43) and infants who were not HIV-exposed (0·17, 0·08-0·33). Serum bactericidal antibody generation following whole-cell pertussis vaccination in infants was not affected. INTERPRETATION: TdaP was safe and immunogenic in pregnant women living with HIV and their infants. TdaP provided superior anti-pertussis toxin IgG concentrations at delivery. Following routine vaccination with whole-cell pertussis vaccine, infants born to women receiving the TdaP vaccine had lower anti-pertussis toxin IgG concentrations than infants born to women receiving Td. In the absence of a correlate of protection against pertussis disease, the clinical significance of this finding is unclear. FUNDING: Medical Research Council Joint Clinical Trials, Canadian Institutes of Health Research, and British Columbia Children's Hospital Research Institute.