Maternal immunization is a safe and effective tool for reducing maternal and perinatal morbidity and mortality from infectious diseases, including tetanus, pertussis, influenza, and COVID-19.(1–4) However, the benefits of immunization to pregnant mothers for emerging infectious pathogens have been significantly delayed given the exclusion or late inclusion of pregnant women in clinical trials evaluating new vaccine candidates. For example, an inactivated influenza vaccine was licensed for the general population in 1945(5) but was not recommended for use during pregnancy until 1960(6) despite high risk of influenza-related severe disease and hospitalization among pregnant women.(7) Additionally, higher morbidity and mortality among pregnant women(8) and their infants was observed early in the COVID-19 pandemic,(1) yet pregnant women were included late in prelicensure trials, and lack of safety data led to low global uptake among pregnant and lactating women compared to the general population.(9) A maternal vaccine for Zika virus infection has not yet been licensed(10) despite a 2015–2016 outbreak leading to congenital defects in infants, leaving the public health community unprepared should another outbreak occur.(11) In addition, uptake of maternal immunization for vaccines known to be safe in pregnancy has been limited in many low- and middle-income countries (LMICs).(12) Context-specific facilitators and barriers to maternal vaccine acceptance are needed to design effective interventions to improve uptake of currently available vaccines and enable expansion of maternal vaccination programs as new vaccines become available.(13)

While the adverse effects of perinatal infections such as influenza, Zika, and COVID-19 have been more visible, the ongoing chronic tuberculosis (TB) pandemic and its effect on maternal and fetal outcomes is under-recognized. It is estimated that TB affects over 200,000 women of childbearing age annually, though the precise global burden of TB among pregnant and postpartum women has not been quantified.(14) TB during pregnancy is associated with unfavorable maternal-infant outcomes including higher risk for maternal morbidity (odds ratio (OR) 2.8, 95% confidence interval (CI) 1.7, 4.6), preterm birth (OR 1.7, 95% CI 1.2, 2.4), low infant birth weight (OR 1.7, 95% CI 1.2, 2.4), and perinatal death (OR 4.2, 95% CI 1.5, 11.8).(15–17) Women experience two-fold higher risk of progression to active TB disease in the first 3–6 months postpartum.(18–20) Maternal TB during pregnancy or postpartum is associated with high rates of infant Mycobacterium tuberculosis infection (19, 21) and an eight-fold higher risk of child mortality among household contacts.(17, 22) With few options to prevent and treat TB during pregnancy and lactation,(23) the World Health Organization (WHO) has identified the development of a TB vaccine that can be administered during pregnancy and lactation as a priority.(24) Ideally, women of childbearing potential would receive a TB vaccine prior to pregnancy; however, adolescents and adult populations have had historically poor vaccine uptake of new vaccines given limited contact points with the healthcare system. Antenatal care and hospitalization for childbirth provide opportunities for immunization, and women should have the option to receive a new TB vaccine during pregnancy or lactation if not previously immunized.(24) Depending on the time to immunogenicity and durability of immunity for new candidate TB vaccines, immunization during pregnancy could prevent maternal progression to TB disease during the postpartum period thereby lowering infant TB exposure, and/or prevent maternal TB and related poor birth outcomes in subsequent pregnancies.(24)

Ethiopia’s national guidelines recommend that pregnant women receive tetanus and diphtheria (Td) vaccination,(25) which has reduced maternal and neonatal tetanus cases nationally by 30%.(2) Despite this progress, maternal tetanus vaccination coverage in the Amhara region has been low, with only 35.7% of women receiving two or more tetanus-containing vaccines during pregnancy.(13) The rollout of COVID-19 vaccination in Ethiopia was expanded in November 2021 to include pregnant women, yet subsequent uptake among pregnant women was around 15% (95% CI 11.7%, 17.3%).(26),(27) Ethiopia has a high incidence of TB at 132 per 100,000 persons (in 2020) and ranks 12^th among the top 30 high TB burden countries.(28) We designed this study to assess facilitators and challenges to uptake of Td vaccination, acceptance of COVID-19 vaccine, and intention to vaccinate against TB during pregnancy and lactation in Amhara, Ethiopia. This study was designed to identify opportunities to optimize current maternal immunization efforts and pave the way for expansion of the maternal immunization pipeline in Ethiopia and similar healthcare systems for high-impact pathogens such as TB.

To our knowledge, this is the first published study to assess acceptability of a future vaccine for TB during pregnancy and lactation. Most women (~90%) intended to receive a TB vaccine while pregnant or lactating, while few women (~40%) were willing to receive a COVID-19 vaccine during pregnancy or lactation. We found reasons cited for receipt of a vaccine during pregnancy centered on the knowledge that vaccines can prevent diseases that may be harmful to a woman’s baby, knowledge of the safety of vaccines in pregnancy, and belief in vaccines’ importance. Participants reported higher perception of TB disease severity compared with COVID-19, consistent with the relative disease burden in Ethiopia. In 2022, TB was ranked as the 5^th leading cause of death in Ethiopia (575 deaths per week) compared to COVID-19’s ranking as 115th (2 deaths per week).(36, 37) Higher vaccine acceptance in an outbreak setting has been observed.(38) In addition, given high rates of Bacille Calmette Guerin (BCG) vaccination at birth in Ethiopia, overall national BCG vaccination coverage in Ethiopia was estimated at 79% in 2019,(39) participants’ prior receipt of BCG or experience vaccinating their children and baseline knowledge of TB may have influenced their willingness to receive a new TB vaccine.(40) While most women in our study were willing to receive a new TB vaccine during pregnancy or lactation, potential barriers to implementation remain. Misinformation around COVID vaccine safety and efficacy was a significant global barrier to vaccine uptake in pregnancy and lactation.(41) Proactive development of tailored vaccine risk communication interventions and identification of trusted messengers to prevent misinformation prior to and during the rollout of new TB vaccines will be critical.(42–45) In addition, identification of health system factors that contribute to discordance between intention to vaccinate and actual receipt of vaccination will be important.(45) Vaseduvan et al. found that while most Tanzanian women surveyed during their 3^rd trimester of pregnancy intended to vaccinate their children, 72% of their children under 2 years had missing or delayed receipt of vaccines, influenced by unexpected health system barriers such as vaccine stock-outs or transportation difficulties.(46, 47) While assessing acceptability of a theoretical vaccine has limitations, understanding potential barriers to vaccine uptake can inform strategic public health messaging prior to vaccine rollout.(48–50)

We found maternal Td uptake in pregnancy was associated with higher maternal education and prior receipt of counseling on vaccines, consistent with other studies in Ethiopia.(34, 51) In contrast, COVID-19 vaccine hesitancy was associated with higher maternal education. In 2022, Abebe et al. found that attaining a higher level of education (college or university degree), was a barrier to COVID-19 vaccine uptake among pregnant women (adjusted odds ratio (aOR) 0.43, 95% CI 0.12, 0.69).(27) Higher education may be associated with access to more information, including misinformation, which has been shown to have a negative impact on COVID-19 vaccine uptake.(42) In other LMICs, COVID-19 vaccine hesitancy in adult populations was found to be slightly higher in those who had attained a higher education (44%, 95% CI 40.2%−46.8%) compared with those who had attained a secondary education (40.9%, 95% CI 38.3%−44.0%) or no or primary education (37.8%, 95% CI 32.5%−41.6%).(52) We also found that living in an urban versus a rural area was associated with COVID-19 vaccine hesitancy. In contrast to our findings, Taye et al. found that urban residence was associated with higher COVID-19 vaccine acceptance among pregnant women in Central Gondar, Ethiopia [aOR 2.03 (95% CI 1.09, 3.77)].(31) In a recent socioeconomic survey, both school enrollment and literacy were found to be higher in urban versus rural locations in Ethiopia.(53) Thus, those living in an urban environment may have attained a higher level of education, had more access to information including misinformation, and may also have higher rates of COVID-19 vaccine hesitancy. The discrepancy in our findings compared to Taye et al. could have been impacted by timing; their study was completed prior to ours and misinformation increased as the pandemic progressed.(42) Our finding that a prior negative experience with a vaccine was associated with Td vaccine uptake suggest confounding by indication, given that prior receipt of a vaccine is necessary to have had a negative experience with vaccination.

We found high acceptability of educational interventions to enhance maternal immunization uptake. To date, there are few intervention trials to target maternal immunization in LMICs, including Ethiopia. Data from upper-middle- and high-income countries have shown the potential for successful interventions to increase maternal vaccination as they relate to provider-to-patient engagement, talking points, educational brochures, posters, lapel buttons, and tablets loaded with patient-centered tutorials.(54, 55) As our study found that health providers were a trusted source for vaccine information, implementing interventions targeted at improving health workers’ knowledge of vaccination and communication skills surrounding immunization could be a successful means to increase maternal vaccination uptake in community campaigns. Our findings and other prior published studies in Amhara suggest educational interventions should address knowledge, attitudes, and beliefs surrounding COVID-19 and TB disease impact in pregnancy and maternal vaccine safety and effectiveness in pregnancy. (27, 31–33) Our study was limited by convenience sampling, which was used to recruit women and may have introduced self-selection or voluntary response bias that could impact the generalizability of our results. Participant responses may also have been influenced by social desirability bias as surveys were conducted at healthcare facilities. Recall bias may have influenced maternal reporting. As our study was only conducted in the Amhara region, the findings may not be generalized to other regions of Ethiopia. We collected data from primary and referral hospitals to optimize participant availability, but this population may not be representative of more rural populations. Differing knowledge of TB and COVID-19 likely impacted our findings, and future studies should evaluate how disease knowledge impacts vaccine acceptance. Finally, direct comparison of maternal acceptability of COVID-19 vaccination and a theoretical TB vaccine may have limited value; assessment of post-licensure acceptability of TB vaccine candidates among pregnant and lactating women will be needed.

We found that most women were willing to receive a TB vaccine, while few were willing to receive a COVID-19 vaccine during pregnancy and lactation. Vaccine-specific knowledge, attitudes, and beliefs were associated with vaccine acceptance. Our findings suggest the importance of evaluating and implementing vaccine-specific, patient-targeted educational interventions and healthcare provider training to strengthen acceptance and uptake of maternal vaccination in pregnancy and lactation. Stakeholders can use such platforms to better plan for the rollout of new maternal vaccines targeting pathogens with a high impact on pregnant women and infants, including TB.