"Why has this new vaccine come and for what reasons?" key antecedents and questions for acceptance of a future maternal GBS vaccine: Perspectives of pregnant women, lactating women, and community members in Kenya.

Group B streptococcus (GBS) is a leading global cause of neonatal sepsis and meningitis, stillbirth, and puerperal sepsis. While intrapartum antibiotic prophylaxis (IAP) is a currently available GBS disease prevention strategy, IAP is programmatically complex to implement, precluding use in low- and middle-income countries. In Kenya, 2% of stillbirths are attributable to GBS infection. Two maternal GBS vaccines are in late-stage clinical development. However, licensure of a maternal GBS vaccine does not translate into reduction of disease. We conducted 28 in-depth interviews with pregnant people, lactating people, and community members across two counties in Kenya to better understand the attitudes and informational needs of primary vaccine beneficiaries. We identified two emerging themes from the data. The first focused on antecedents to maternal GBS vaccine acceptability. The most common antecedents focused on the vaccine's ability to protect the baby and/or the mother, followed by community sensitization before the vaccine was available. The second key theme focused on questions that would need to be addressed before someone could accept a maternal GBS vaccine. Three key categories of questions were identified, including vaccine safety compared to vaccine benefits, who gets the vaccine, and how the vaccine works. Realizing the potential benefits of a future GBS maternal vaccine will require a multifactorial approach, including ensuring that communities are aware of GBS-related harms as well as the safety and effectiveness of a maternal GBS vaccine. Our study contributes to informing this multifactorial approach by elucidating the attitudes and concerns of key populations.

Understanding Kenyan policymakers' perspectives about the introduction of new maternal vaccines.

New vaccine policy adoption is a complex process, especially in low-and-middle-income countries (LMICs), requiring country policymakers to navigate challenges such as competing priorities, human and financial resource constraints, and limited logistical capacity. Since the Expanded Programme on Immunization's (EPI) beginning, most new vaccine introductions under this structure have not been aimed at adult populations. The majority of adult vaccines offered under the EPI are not typically tested among and tailored for pregnant persons, except those that are specifically recommended for pregnancy. Given that new maternal vaccines, including RSV and GBS vaccines, are on the horizon, it is important to understand what barriers may arise during the policy development and vaccine introduction process. In this study, we sought to understand information needs among maternal immunization policymakers and decision-makers in Kenya for new vaccine maternal policy adoption through in-depth interviews with 20 participants in Nakuru and Mombasa counties in Kenya. Results were mapped to an adapted version of an established framework by Levine et al., (2010) focused on new vaccine introduction in LMICs. Participants reported that the policy process for new maternal vaccine introduction requires substantial evidence as well as coordination among diverse stakeholders. Importantly, our findings suggest that the process for new maternal vaccines does not end with the adoption of a new policy, as intended recipients and various actors can determine the success of a vaccine program. Previous shortcomings, in Kenya, and globally during HPV vaccine introduction show the need to allocate adequate resources in education of communities given the sensitive target group. With maternal vaccines targeting a sensitive group - pregnant persons- in the pipeline, we are at an opportune time to understand how to ensure successful vaccine introduction with optimal acceptance and uptake, while also addressing vaccine hesitancy to increase population benefit.

Sources of COVID-19 Vaccine Promotion for Pregnant and Lactating Women in Bangladesh.

COVID-19 vaccines are an effective public health intervention to reduce COVID-19-related morbidity and mortality. Given that pregnant and lactating women have a higher risk of severe COVID-19 complications, it is paramount to understand the factors that inform vaccine decision-making among this population. In this study, we sought to identify facilitators and barriers to COVID-19 vaccine acceptance and vaccine promotion in pregnant and lactating women in Bangladesh. We conducted 40 in-depth interviews with 12 pregnant women, 12 lactating women, and 16 health workers from one urban and four rural communities in Bangladesh. We used a grounded theory approach to identify emerging themes. Our results suggest that health workers and religious leaders played key roles in promoting COVID-19 vaccines in this population. Further, we found that the culture of trust in public health authorities and the existing vaccine infrastructure facilitated vaccine promotion. However, changes in vaccine eligibility and myths and rumors acted as both facilitators and barriers to vaccine promotion within our study. It is crucial that maternal immunization vaccine promotion efforts push pregnant and lactating women toward vaccine acceptance to protect the health of mothers and their babies. Additionally, as new maternal vaccines are developed and licensed, understanding how to best promote vaccines within this group is paramount.

COVID-19 vaccine decision-making among pregnant and lactating women in Bangladesh.

Pregnant and lactating women's vaccine decision-making process is influenced by many factors. Pregnant women were at increased risk for severe disease and poor health outcomes from COVID-19 at various time points during the pandemic. COVID-19 vaccines have been found to be safe and protective during pregnancy and while breastfeeding. In this study, we sought to examine key factors that informed the decision-making process among pregnant and lactating women in Bangladesh. We conducted 24 in-depth interviews, with 12 pregnant and 12 lactating women. These women were from three communities in Bangladesh: one urban community, and two rural communities. We used a grounded theory approach to identify emerging themes and organized emerging themes using a socio-ecological model. The socio-ecological model suggests that individuals are influenced by many levels, including individual-level influences, interpersonal-level influences, health care system-level influences, and policy-level influences. We found key factors at each socio-ecological level that influenced the decision-making process of pregnant and lactating women, including perceived benefits of vaccines and vaccine safety (individual-level), the influence of husbands and peers (interpersonal-level), health care provider recommendations and vaccine eligibility (health care system-level), and vaccine mandates (policy-level). As vaccination can reduce the effect of COVID-19 disease in mothers, infants, and unborn children, targeting critical factors that inform the decision-making process is paramount for improving vaccine acceptance. We hope the results of this study will inform vaccine acceptance efforts to ensure that pregnant and lactating women take advantage of this life-saving intervention.

COVID-19 vaccine acceptance among Bangladeshi adults: Understanding predictors of vaccine intention to inform vaccine policy.

OBJECTIVES: The purpose of this study was to identify predictors of COVID-19 vaccine intention among Bangladeshi adults. METHODS: Secondary data from the COVID-19 Beliefs, Behaviors & Norms Survey conducted by the Massachusetts Institute of Technology (MIT) and Facebook were analyzed. Data were collected from 2,669 adult Facebook users in Bangladesh and was collected between February 15 and February 28, 2021. Binomial logistic regression examined the relationship between COVID-19 vaccination intent and demographic variables, risk perception, preventive behaviors, COVID-19 knowledge, and likelihood of future actions. RESULTS: Seventy-nine percent of respondents reported intent to get the COVID-19 vaccine when it becomes available. Intent to get vaccinated was highest among females, adults aged 71-80, individuals with college or graduate-level degrees, city dwellers, and individuals who perceived that they were in excellent health. Results of the binomial logistic regression indicated that predictors of vaccination intent include age (OR = 1.39), high risk perception of COVID-19 (OR = 1.47), and intent to practice social distancing (OR = 1.22). DISCUSSION: Findings suggest that age, perceived COVID-19 risk, and non-pharmaceutical COVID-19 interventions may predict COVID-19 vaccination intent among Bangladeshi adults. Findings can be used to create targeted messaging to increase demand for and uptake of COVID-19 vaccines in Bangladesh.

Conceptualizing the COVID-19 Pandemic: Perspectives of Pregnant and Lactating Women, Male Community Members, and Health Workers in Kenya.

Pregnant women are at greater risk of adverse outcomes from SARS-CoV-2 infection. There are several factors which can influence the ways in which pregnant women perceive COVID-19 disease and behaviorally respond to the pandemic. This study seeks to understand how three key audiences-pregnant and lactating women (PLW), male community members, and health workers-in Kenya conceptualize COVID-19 to better understand determinants of COVID-19 related behaviors. This study used qualitative methods to conduct 84 in-depth interviews in three counties in Kenya. Data were analyzed using a grounded theory approach. Emerging themes were organized based on common behavioral constructs thought to influence COVID-19 related behaviors and included myths, risk perception, economic implications, stigma, and self-efficacy. Results suggest that risk perception and behavioral attitudes substantially influence the experiences of PLW, male community members, and health workers in Kenya during the COVID-19 pandemic. Public health prevention and communication responses targeting these groups should address potential barriers to preventive health behaviors, such as the spread of misinformation, financial constraints, and fear of social ostracization.

A socio-ecological exploration to identify factors influencing the COVID-19 vaccine decision-making process among pregnant and lactating women: Findings from Kenya.

The vaccine decision-making process of pregnant and lactating women is complex. Regarding COVID-19, pregnant women are at increased risk for severe disease and poor health outcomes. While pregnant and lactating women were excluded from COVID-19 vaccine trials, available evidence suggests that COVID-19 vaccines are safe and protective during pregnancy. In this study, we used a socio-ecological approach to explore factors influencing the decision-making process for COVID-19 vaccines in pregnant and lactating women in Kenya, for the purpose of informing demand generation strategies. As pregnant and lactating women are influenced by many factors, we conducted 84 in-depth interviews with a variety of stakeholders, including 31 pregnant or lactating women, 20 healthcare workers such as nurses, midwives, doctors, and frontline workers, 25 male family members of pregnant or lactating women, and 8 gatekeepers such as community leaders and faith-based leaders. These individuals were recruited from six communities in Kenya: three urban, and three rural. We applied a grounded theory approach to identify emerging themes and organized emerging themes using the SAGE Vaccine Hesitancy model, which includes three categories of determinants of vaccine acceptance, including contextual influences, individual and group influences, and vaccine and vaccination specific issues. Myths, interpersonal norms, and religion emerged as themes related to contextual influences. Safety, risk perception, and the role of the healthcare worker emerged as themes related to individual and group influences. For vaccine and vaccination specific issues, emerging themes included availability, accessibility, and eligibility. While maternal immunization can substantially reduce the effect of infectious diseases in mothers and infants, vaccine acceptance is critical. However, vaccines do not save lives; vaccination does. We hope the results of this study can be used to tailor communication efforts to increase vaccine demand among pregnant and lactating women.

Lack of clear national policy guidance on COVID-19 vaccines influences behaviors in pregnant and lactating women in Kenya.

SARS-CoV-2 infection in pregnancy is associated with a greater risk of maternal and newborn morbidity and maternal death. In Kenya, pregnant and lactating women (PLW) were ineligible to receive COVID-19 vaccines until August 2021. How shifts in policy influence vaccine behaviors, such as health worker recommendations and vaccine uptake, is not well documented. We conducted qualitative interviews with PLW, health workers, and policymakers in Kenya to understand how different stakeholders' perceptions of national policy regarding COVID-19 vaccination in pregnancy shaped vaccine behaviors and decision-making. Policymakers and health workers described pervasive uncertainty and lack of communication about the national policy, cited vaccine safety as their primary concern for administering COVID-19 vaccines to PLW, and expressed that PLW were inadequately prioritized in the COVID-19 vaccine program. PLW perceived the restrictive policy as indicative of a safety risk, resulting in vaccine hesitancy and potentially exacerbated inequities in vaccine access. These findings support the need for the development and dissemination of effective vaccine communication guidelines and the prioritization of PLW in COVID-19 vaccination policies and campaigns. To ensure PLW do not face the same inequities in future epidemics, data on infectious disease burdens and vaccine uptake should be collected systematically among pregnant women, and PLW should be included in future vaccine trials.

The crystal structure of the D-alanine-D-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding.

Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

Long-term memory (LTM) formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose) polymerase-1 (PARP-1), are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP) in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosyl)ation (PAR) dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP) ribose molecules (pADPr) after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA) and extracellular signal-regulated kinase (ERK)--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I), responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components)--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.