The safety and immunogenicity of vaccines administered to pregnant women living with HIV: a systematic review and meta-analysis.

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: This work was funded by Medical Research Council Joint Clinical Trials Round 9 [MR/T004983/1].

Vaccine value profile for Klebsiella pneumoniae.

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. 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. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Vaccine value profile for Group B streptococcus.

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.

Antibody and B-cell Immune Responses Against Bordetella Pertussis Following Infection and Immunization.

Neither immunization nor recovery from natural infection provides life-long protection against Bordetella pertussis. Replacement of a whole-cell pertussis (wP) vaccine with an acellular pertussis (aP) vaccine, mutations in B. pertussis strains, and better diagnostic techniques, contribute to resurgence of number of cases especially in young infants. Development of new immunization strategies relies on a comprehensive understanding of immune system responses to infection and immunization and how triggering these immune components would ensure protective immunity. In this review, we assess how B cells, and their secretory products, antibodies, respond to B. pertussis infection, current and novel vaccines and highlight similarities and differences in these responses. We first focus on antibody-mediated immunity. We discuss antibody (sub)classes, elaborate on antibody avidity, ability to neutralize pertussis toxin, and summarize different effector functions, i.e. ability to activate complement, promote phagocytosis and activate NK cells. We then discuss challenges and opportunities in studying B-cell immunity. We highlight shared and unique aspects of B-cell and plasma cell responses to infection and immunization, and discuss how responses to novel immunization strategies better resemble those triggered by a natural infection (i.e., by triggering responses in mucosa and production of IgA). With this comprehensive review, we aim to shed some new light on the role of B cells and antibodies in the pertussis immunity to guide new vaccine development.

Indirect effects of COVID-19 on maternal, neonatal, child, sexual and reproductive health services in Kampala, Uganda.

BACKGROUND: COVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown that restricted individuals' movements in Uganda limited access to services. METHODS: An observational study, using routinely collected data from Electronic Medical Records, was carried out, in Kawempe district, Kampala. An interrupted time series analysis assessed the impact on maternal, neonatal, child, sexual and reproductive health services from July 2019 to December 2020. Descriptive statistics summarised the main outcomes before (July 2019-March 2020), during (April 2020-June 2020) and after the national lockdown (July 2020-December 2020). RESULTS: Between 1 July 2019 and 31 December 2020, there were 14 401 antenatal clinic, 33 499 deliveries, 111 658 childhood service and 57 174 sexual health attendances. All antenatal and vaccination services ceased in lockdown for 4 weeks.During the 3-month lockdown, the number of antenatal attendances significantly decreased and remain below pre-COVID levels (370 fewer/month). Attendances for prevention of mother-to-child transmission of HIV dropped then stabilised. Increases during lockdown and immediately postlockdown included the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low-birth-weight and premature infant births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable. Immunisation clinic attendance declined while neonatal death rate rose (from 39 to 49/1000 livebirths). The number of children treated for pneumonia, diarrhoea and malaria decreased during lockdown. CONCLUSION: The Ugandan response to COVID-19 negatively impacted maternal, child and neonatal health, with an increase seen in pregnancy complications and fetal and infant outcomes, likely due to delayed care-seeking behaviour. Decreased vaccination clinic attendance leaves a cohort of infants unprotected, affecting all vaccine-preventable diseases. Future pandemic responses must consider impacts of movement restrictions and access to preventative services to protect maternal and child health.

Relative impact of pre-eclampsia on birth weight in a low resource setting: A prospective cohort study.

OBJECTIVES: Low birth-weight is a major risk factor for perinatal death in sub-Saharan Africa, but the relative contribution of determinants of birth-weight are difficult to disentangle in low resource settings. We sought to delineate the relationship between birth-weight and maternal pre-eclampsia across gestation in a low-resource obstetric setting. STUDY DESIGN: Prospective cohort study in a tertiary referral centre in urban Uganda, including 971 pre-eclampsia cases and 1461 control pregnancies between 28 and 42 weeks gestation. MAIN OUTCOME MEASURES: Nonlinear modeling of birth-weight versus maternal pre-eclampsia status across gestation. Models were adjusted for maternal-fetal characteristics including maternal age, parity, HIV status, and socio-economic status. Propensity score matching was used to control for the severity of pre-eclampsia at different gestational ages. RESULTS: Mean birth-weight for pre-eclampsia cases was 2.48 kg (±0.81SD) compared to 3.06 kg (±0.46SD) for controls (p < 0.001). At 28 weeks, the mean birth-weight difference between pre-eclampsia cases and controls was 0.58 kg (p < 0.05), narrowing to 0.17 kg at 39 weeks (p < 0.01). Controlling for pre-eclampsia severity only partially explained this gestational difference in mean birth-weight between pre-eclampsia cases and controls. Holding gestational age constant, pre-eclampsia status predicted 7.1-10.5% of total variation in birth-weight, compared to 0.05-0.7% for all other maternal-fetal characteristics combined. CONCLUSIONS: Pre-eclampsia is the dominant predictor of birth-weight in low-resource settings and hence likely to heavily influence perinatal survival. The impact of pre-eclampsia on birth-weight is smaller with advancing gestational age, a difference that is not fully explained by controlling for pre-eclampsia severity.