Background: We investigated pregnant women, community leaders, healthcare workers (HCWs) and programme managers’ perceptions of maternal vaccination in Kampala, Uganda. Methods: We conducted focus group discussions, key informant interviews and in-depth discussions with HCWs (3), community leaders (3), pregnant women (8) and programme managers (10) between November 2019 and October 2020. Data were analysed thematically. Results: Pregnant women, community leaders and some HCWs had limited maternal immunisation knowledge. There was confusion over what constitutes a vaccine. Pregnant women may not receive vaccines because of mistrust of government; use of expired vaccines; reliance on traditional medicine; religious beliefs; fear of side effects; HCWs attitudes; and logistical issues. The key facilitators of maternal vaccination were a desire to prevent diseases, positive influences from HCWs and information about vaccine side effects. Community leaders and some pregnant women highlighted that pregnant women do not make decisions about maternal vaccination independently and are influenced by different individuals, including other pregnant women, older people, partners, relatives (parents), community leaders, HCWs and the government. Conclusions: Our results indicate that public health messaging should target all community members, including partners and parents of pregnant women as well as HCWs, to improve knowledge of and confidence in maternal vaccines.

Background Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure. Objectives The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design. Design Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018). Setting Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales. Participants Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria. Interventions No interventions were performed. Main outcome measures (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus. Results A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V). Limitations Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants. Conclusions We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study. Future work A large case–control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended. Trial registration Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information.

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)

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonisation, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK, and were sampled every two weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. 70 women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonised with GBS than in non-colonised, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimisation of immunoassays to measure GBS-CPS specific antibodies. The difference between the dynamics of colonisation and antibody response is interesting and further investigation is required for vaccine development.