Group B streptococcus (GBS) is a major global cause of neonatal meningitis, sepsis and pneumonia, with an estimated 91,000 infant deaths per year and an additional 46,000 stillbirths. GBS infection in pregnancy is also associated with adverse maternal outcomes and preterm births. As such, the World Health Organization (WHO) prioritised the development of a GBS vaccine suitable for use in pregnant women and use in LMICs, where the burden of disease is highest. Several GBS vaccines are in clinical development. The WHO Defeating Meningitis by 2030 has set a target of 2026 for vaccine licensure. This 'Vaccine Value Profile' (VVP) for GBS is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO regions of AFR, AMR, EUR, WPR. All contributors have extensive expertise on various elements of the GBS VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Human Immunodeficiency Virus (HIV)-exposed uninfected (HEU) infants have a higher burden of infectious diseases related morbidity and mortality compared with HIV-unexposed uninfected (HUU). Immunization of pregnant women living with HIV (PWLWH) could reduce the severity and burden of infectious diseases for HEU in early infancy. We conducted a systematic review of safety and immunogenicity of vaccines administered to PWLWH and meta-analyses to test the overall effect of immunogenicity comparing pregnant women without HIV (PWWH) to PWLWH. We searched MEDLINE, Embase, Web of Science, Virtual Health Library and Cochrane databases in accordance with PRISMA guidelines for randomized controlled trials and observational studies. Review articles, case series, conference abstracts, and animal studies were excluded. Studies were included from inception to 6th September 2023, with no language restrictions. Random effects meta-analyses were performed for immunogenicity using Review manager (RevMan) analysis software version 5.4.1, Geometric Mean Titer (GMT) values were transformed to obtain the mean and standard deviation within RevMan, the effect size was computed and reported as mean difference with respective 95% confidence intervals. The review was registered with PROSPERO CRD42021289081. We included 12 articles, comprising 3744 pregnant women, 1714 were PWLWH given either influenza, pneumococcal or an investigational Group B streptococcal (GBS) vaccine. Five studies described safety outcomes, and no increase in adverse events was reported in PWLWH compared to PWWH. The GMT increase from baseline to 28–35 weeks post vaccination in HA units ranged from 12.4 (95% CI: 9.84–14.9) to 238.8 (95% CI: 0.35–477.9). Meta-analyses of influenza vaccines showed the pooled geometric mean difference in Hemagglutination Inhibition (HAI) titers post vaccination was 56.01 (95% CI: 45.01–67.01), p < 0.001. The increase was less in PWLWH when compared with PWWH: −141.76 (95% CI: −194.96, −88.55), p < 0.001. There are limited data on the safety and immunogenicity of vaccines given to PWLWH making policy consideration in this group difficult when new vaccines are introduced. With new vaccines on the horizon, PWLWH need to be included in studies to promote vaccine confidence for this special population. This work was funded by 10.13039/501100000265 Medical Research Council Joint Clinical Trials Round 9 [MR/T004983/1].

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. 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. 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. 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. Medical Research Council Joint Clinical Trials, Canadian Institutes of Health Research, and British Columbia Children's Hospital Research Institute.

Introduction: Vaccination is a key strategy to safeguard the health of pregnant women and newborns. Although vaccine acceptance is often higher in low- and middle-income countries, the COVID-19 pandemic has highlighted increasing vaccine hesitancy. Vaccine hesitancy, specifically in pregnant women, must be understood to increase uptake. We used data from a Ugandan pregnancy registry study to examine sociodemographic factors linked to uptake of vaccines (tetanus toxoid and later COVID-19) in pregnancy. Methods: Pregnant women were recruited in Kampala, Uganda, as part of the PREPARE (Prevention of invasive Group B Streptococcus disease in young infants: a pathway for the evaluation & licensure of an investigational maternal GBS vaccine) study from September 1, 2020 until February 24, 2022. Demographic, socioeconomic and obstetric data were collected alongside COVID-19 and tetanus vaccination. Results: One thousand five hundred sixty-eight participants were included: 151 (10%) were unvaccinated, 11 (1%) received COVID-19 vaccine only, 1230 (78%) received a tetanus vaccine only and 176 (11%) received both. Lower vaccination rates were seen in participants attending fewer than 4 antenatal care episodes ( P < 0.001), and those with higher parity ( P = 0.036). Higher vaccination rates were seen with a managerial or professional occupation or higher maternal education level, but paternal occupation was not significantly associated with maternal vaccination. Parish vaccination rates varied from 0% to 100%, with 49 (29%) of parishes showing a vaccination rate <90%. Conclusions: This study highlights antenatal care as a key route for health promotion, and the stark difference in uptake between new and established antenatal vaccines. Further qualitative studies should investigate effective interventions to establish the safety and benefit of newer maternal vaccines across all demographic groups.

Background: Globally there are an estimated 24.1 million cases and 160,700 deaths from pertussis annually in children under five years. The disease burden is higher in low- and middle-income countries, especially the African region, which contributes the largest proportions of cases and deaths. Immunization against pertussis in pregnancy is a recommended strategy for the prevention of infant pertussis in many high-income countries. However, vaccine immunogenicity and effectiveness may be different in immunocompromised individuals such as women living with HIV. There is a need to generate data on the impact of HIV infection in pregnancy on maternal and infant immunity to vaccines against pertussis. Methods: This is a phase II, randomized controlled observer blind clinical trial of 100 women living with HIV and 100 uninfected women randomized to either standard vaccines (tetanus diphtheria vaccine, Td) or a tetanus diphtheria-pertussis vaccine (Tdap). Participants aged 18-40 years carrying a low-risk singleton pregnancy with a gestational age between 16 and 26 weeks confirmed on ultrasound scan, with no history of receipt of tetanus or pertussis vaccines in the current pregnancy will be recruited. Women will receive either two doses of Td or a first dose of Td and second dose of Tdap vaccine. Participants will complete 14-day diary cards to monitor reactogenicity. Mother-infant dyads will be followed up until the infant is one year old. The outcomes include: safety for the pregnant woman and infant; anti-pertussis toxin (PT) and anti-filamentous haemagglutinin (FHA) IgG concentrations in maternal, cord and infant blood and breastmilk, compared by maternal HIV status. Discussion: This study will investigate whether vaccines given to women living with HIV have similar immunogenicity and reactogenicity to vaccines given to pregnant women without HIV and monitor the effect of Tdap in pregnancy on infant immune responses. clinicalTrials.gov registration: NCT04589312 (19/10/2020)