Perception of a novel Group B Streptococcus Vaccine Among Pregnant and Lactating Individuals

Abstract

Background

Multivalent conjugate GBS vaccines are in development for use in pregnancy. We aimed to understand perceptions of a novel GBS vaccine among pregnant and lactating persons following the COVID vaccine experience.

Methods:

As part of an ongoing survey-based prospective cohort study, we conducted a follow-up survey with questions about GBS knowledge and acceptability of clinical trial participation for a novel GBS vaccine. Participants in this IRB-exempt study completed surveys via REDCap survey online.

Results:

Among 14,903 participants who completed the follow-up survey, 1,785 were pregnant, 6,661 were lactating and 6,457 were either recently pregnant or lactating or planning for pregnancy. Pregnant individuals were less likely to report that they would likely or extremely likely participate in a clinical trial for a GBS vaccine during pregnancy compared to people who were neither pregnant nor lactating (p<0.001). In contrast, lactating individuals were more likely to report that they would likely or extremely likely participate in a clinical trial for a novel GBS vaccine in lactation compared to people who were neither pregnant nor lactating (p<0.001). Most participants preferred protein based (n=10,214, 70.5%) and mRNA-based (n=10354, 71.5%) vaccine platforms for GBS vaccines.

Conclusions:

Overall, our participants expressed a good understanding of GBS. There is a mixed acceptability of participation in a novel GBS vaccine clinical trial during pregnancy with a greater acceptability during lactation. The perspective of pregnant and lactating people is critically relevant as new vaccines are developed.

INTRODUCTION

Streptococcus agalactiae or Group B streptococcus (GBS) can colonize the genitourinary (GU) and gastrointestinal (GI) tract of pregnant people and lead to adverse pregnancy, maternal and neonatal outcomes (1, 2). GBS infection is a significant contributor to early-onset neonatal sepsis and mortality, particularly in low-income countries (1), as well as significant neurodevelopmental impairment among those surviving GBS illness (3). Intrapartum antibiotic prophylaxis is currently the primary preventative strategy to reduce the risk of neonatal GBS early onset disease (EOD) (2). This preventative strategy, only available in higher income countries with varying uptake globally, is not effective at preventing neonatal late-onset disease and adverse maternal and pregnancy outcomes (2).

Maternal immunization is a strategy to vaccinate pregnant people to prevent or minimize morbidity and mortality related to infectious pathogens for pregnant people, their fetuses and infants (4). Given the severity of adverse events associated with perinatal GBS infection, it is a high priority target for vaccine development (5). Several maternal GBS vaccine candidates are in development that may address the limitations of current prevention strategies (6). One recent multivalent candidate for a GBS vaccine demonstrated favorable safety profile in a phase 1/2 clinical trial. (7)

While maternal immunization may present an option to increase transfer of maternally-derived immune protection to the infant, vaccine uptake of already approved vaccines among the pregnant community is not optimal (8). In fact, a recent study by Razzahi et al.(8) demonstrated that vaccine uptake in pregnancy has decreased since the COVID-19 pandemic. Given the development of a GBS vaccine along with increasing vaccine hesitancy among pregnant people, our study aimed to investigate the perception of a novel GBS vaccine among people who were pregnant, lactating or planning pregnancy and who received a COVID-19 vaccine in the early months of the COVID-19 roll-out.

MATERIALS AND METHODS

In January 2021, we launched an online prospective cohort study of people who were predominately pregnant, lactating or either recently pregnant or planning pregnancy at the time of the approval of the COVID-19 vaccine. Participants were recruited and enrolled by snowball sampling and chain-referral as previously described (9). A follow up survey was sent to the participants in May 2022, that included questions regarding self-reported knowledge of and experience with GBS infection and perception of GBS vaccine. The online survey was conducted on REDCap (version 12.1.1, 2022). This study was IRB-exempt by the University of Washington Human Subjects Division. The analysis was completed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (10).

Variables

The original survey collected baseline demographic and background data, including age, gravidity, parity, education level and area of employment as previously reported (9). The follow up survey asked participants about GBS knowledge, including questions about familiarity, experience, and perception of seriousness of infection in pregnant people and neonates. In addition, we asked participants about their willingness to participate in clinical trials for a novel GBS vaccine while pregnant or lactating as well as acceptable vaccine platforms for the clinical trials. (See Survey, Supplemental Digital Content1)

Analysis

We grouped participants based on whether they were pregnant, lactating or recently pregnant or planning pregnancy (neither pregnant nor lactating) at the time of the follow up survey. We compared baseline characteristics between the groups using chi-square test for categorical variables or one-way analysis of variance for continuous variables. We used multivariable logistic regression models to compare knowledge of and experience with GBS along with opinions about participation in novel GBS vaccine clinical trials and preferred vaccine platforms for novel GBS vaccines between individuals who were pregnant to those who were neither pregnant nor lactating, and between individuals who were lactating to those who were neither pregnant nor lactating at the time of the follow up survey. For the multivariable logistic regression analyses, knowledge of GBS was defined as good understanding or higher compared to never heard of it or no detailed knowledge. Experience with GBS was defined as any experience versus none. We defined willingness to participate in a clinical trial as likely or extremely likely. We also conducted secondary analyses comparing responses to vaccination questions between those with a good understanding of GBS compared to none and those with experience with GBS compared to those with none. All multivariable models were adjusted for group differences with respect to age, parity, and area of work. We performed statistical analyses using STATA 18.0 (College Park, TX) (11).

RESULTS

There were 14,905 participants, 1,785 (12.0%) of whom were pregnant, 6,661 (44.7%) were lactating and 6,459 (43.3%) were neither pregnant nor lactating, that responded to the follow up survey from May 2022 to April 2023. Most respondents identified as female (99.7%), White (92.8%) and non-Hispanic (94.5%). Most people lived in the United States (96.7%), held a Master or Professional degree (66.6%) and worked in healthcare (55.5%) (see Table, Supplemental Digital Content 2).

Participants reported either a good (n=7,148, 48.0%) or moderate (n=5,222, 35.1%) understanding of GBS and GBS infection. Most respondents associated GBS infection in a neonate or infant as ‘life-threatening’ (n= 8,488, 57.0%) however they viewed GBS infection in a pregnant person as ‘mild’ (n= 6,297, 42.4%). Fewer pregnant individuals reported that they would be likely or extremely likely to participate in a clinical trial for a novel GBS vaccine during pregnancy or during lactation compared to participants who were neither pregnant nor lactating (both p<0.001), while higher numbers of participants who were lactating reported that they would be likely or extremely likely to participate in a novel GBS vaccine clinical trial while lactating compared to people who were neither pregnant nor lactating (p<0.001). Despite this, 28.6% of pregnant participants did indicate that they would be likely or extremely likely to consider participating in clinical trials for a novel GBS vaccine. Most participants preferred protein based (n=10,214, 70.5%) and mRNA-based (n=10354, 71.5%) vaccine platforms for the GBS vaccine (see Table, Supplemental Digital Content 3).

In the multivariable regression analyses, pregnant and lactating individuals were more likely to have a good understanding of GBS and GBS infection compared to those participants that were neither pregnant nor lactating (adjusted odd ratio [aOR] 1.19, 95% Confidence Interval [CI] 1.07, 1.33; p=0.002 and aOR 1.27, CI 1.18,1.36; p<0.001, respectively). Similarly pregnant and lactating individuals were also more likely to have had experience with GBS infection compared to those that were neither pregnant nor lactating (aOR 1.15, CI 1.01, 1.31; p=0.04 and aOR 1.36 CI 1.25,1.48; p<0.001, respectively). Pregnant participants were less likely to consider being part a of clinical trial for GBS vaccine during pregnancy (aOR 0.69 CI 0.61, 0.78; p<0.001) or when lactating (aOR 0.72 CI 0.64, 0.80; p<0.001) compared to participants that were neither pregnant nor lactating. There was no difference between lactating participants and participants who were neither pregnant nor lactating on whether they would participate in a clinical trial for GBS vaccine while lactating however lactating individuals were less like to participate if pregnant (aOR 0.93 CI 0.86, 1.00; p=0.05). Lastly, pregnant people were more likely to select the option that no vaccine platform would be acceptable for participation in an GBS clinical trial (aOR 1.59 CI 1.41, 1.79; p<0.001) compared to participants that were neither pregnant nor lactating. While lactating individuals were more likely to select a protein-based (aOR 1.13 CI 1.04, 1.22; p=0.003) or mRNA-based platform (aOR 1.09 CI 1.01, 1.18; p=0.03) when compared to people that are neither pregnant nor lactating (see Table, Supplemental Digital Content 4).

A sub-analysis was completed comparing responses to participation in GBS vaccine clinical trial based on little to no understanding of GBS to good understanding of GBS. Participants with a good understanding of GBS were more likely or extremely likely to participate in a GBS vaccine clinical trial while pregnant (p<0.001) or lactating (p<0.001) compared to those with little to no understanding to GBS (data available in Table, Supplemental Digital Content 5). Additionally, participants with a good understanding of GBS were like less likely to select the option that no vaccine platform would be acceptable for participation in a GBS vaccine clinical trial (p<0.001). Lastly, another sub-analysis was completed comparing responses to participation in GBS vaccine clinical trial based on experience with GBS infection versus no experience with GBS infection. Participants with GBS experience were more likely and extremely likely to participate in a GBS vaccine clinical trial while pregnant (p<0.001) or lactating (p<0.001) compared to participants without GBS experience. Similarly, people with GBS experience were also significantly less likely to select the option that no vaccine platform would be acceptable for participation in a GBS vaccine clinical trial (p<0.001) compared to people with no GBS experience. (Data available in Table, Supplemental Digital Content 6)

DISCUSSION

Participants in our relatively educated cohort overall reported a moderate to good understanding of GBS and GBS infection, with many respondents associating the infection in the neonate as ‘life-threatening’ compared to ‘mild’ in a pregnant person. Pregnant and lactating individuals reported a better understanding of GBS and GBS infection and were more likely to have had experience with GBS when compared to those who were neither pregnant nor lactating in our cohort. Similarly, pregnant, and lactating participants were more likely to have had experience with GBS infection when compared to those that were neither pregnant nor lactating. There is mixed acceptance for willingness to participate in clinical trials for a novel GBS vaccine while pregnant with more acceptance during lactation. Respondents with knowledge of or experience with GBS reported a higher willingness to participate in clinical trials for a novel GBS vaccine while pregnant or lactating compared to participants with little or no GBS knowledge or experience.

Our findings are like other studies investigating a hypothetical licensed GBS vaccine in pregnancy. In their study in the United States, Dempsey et al. found higher acceptability of receiving a GBS vaccine in pregnancy in recently pregnant individuals, with 79% of individuals reporting they would “definitely” or “probably” have gotten a GBS vaccine in their recent pregnancy if available (12). Similarly, McQuaid et al.(13) found that among 1013 women 18–44 years old in the United Kingdom, participants with children were more likely to know of GBS and consider taking part in a GBS vaccine clinical trial. In studies evaluating COVID-19 vaccine attitudes, confidence in vaccine safety and perceived effectiveness of the vaccine led to increased rates of vaccine acceptance, indicating a likely similar trend with novel GBS vaccines (14, 15). Regarding specific knowledge about GBS vaccines, Geoghegan et al. found that among Irish and US participants, perceived infant benefit from a GBS vaccine was the most important driver for vaccine acceptance, indicating that education and knowledge of the risks of GBS in pregnancy are currently lacking yet imperative for this future vaccine (16). In their Australian study in 2019, Giles et al. found that 63% of pregnant participants had no knowledge of GBS, concluding that “an enormous amount of work” would have to be done to educate this population and thus increase acceptance and coverage of a GBS vaccine (17). Like the challenges surrounding COVID-19 vaccines in pregnant persons, GBS vaccination campaigns will need to implement multilevel interventions to educate healthcare providers and the target population to improve novel vaccine uptake in pregnant and lactating individuals (14, 18, 19). Unlike the introduction of COVID-19 vaccines in the setting of a public health emergency, novel GBS vaccines will be tested on pregnant persons through clinical trials, highlighting that understanding the perceptions of pregnant and lactating persons will be integral to the designs of these studies. (16).Prior research indicates that about 30% of pregnant individuals accept novel vaccines in pregnancy, including the COVID-19 vaccine (20, 21), which is like the number of pregnant individuals in our study indicating that they would likely participate in a GBS clinical trial. Positive perceptions of a GBS vaccine during pregnancy may correlate with higher acceptance of this vaccine, as seen with the COVID-19 vaccine (15), and, once licensed, may lead to a significant reduction in incidence of GBS-related neonatal morbidity and mortality. Intrapartum antibiotic prophylaxis is the standard prevention strategy (2), but a GBS vaccine could provide a more cost-effective and long-lasting solution (22). Healthcare cost reduction associated with a GBS vaccine has been estimated at approximately $385 million, including elimination of hospitalizations, intensive care admissions, and long-term medical care for affected infants (22). In settings where access to healthcare resources and antibiotics may be limited, this vaccine could have significant implications for reducing antibiotic resistance, severe maternal allergic reactions and the negative impact on the pediatric microbiome (2).

Information on public perceptions of GBS infections and the GBS vaccine is important to support further research in clinical trials and implementation of vaccines once approved. For example, data on vaccine platform preference in this specific population may be useful for clinical trials. In our study, most of the participants indicated a preference for protein-based or mRNA-based vaccines. Further research into understanding GBS vaccine perception and factors that can alter this perception may also be important to prenatal health providers who will be tasked with counseling and recommending a GBS vaccine in the future. While the survey data provides encouraging results for future GBS vaccine research, knowledge gaps essential for GBS vaccine implementation remain including maternal benefit, cost-effectiveness, and cultural acceptance (5).

Strengths and Limitations

Strengths of our study include a large cohort of individuals who responded to our survey and who were concurrently pregnant, lactating or recently pregnant or lactating. Our participants were of similar age, reproductive potential, and fertility intentions. In addition, our large sample size included participants from all 50 states and 3 of 5 territories of the United States. We have published prior findings on the primary COVID-19 vaccine series and booster dose from the same cohort previously (9, 23).

Limitations of our study include the convenience sample of our participants during the initial COVID-19 vaccine roll-out beginning in January 2021, which was comprised of a large percentage of healthcare workers and vaccine accepting participants who were able to self-administer an English language online survey. In addition, experience with GBS and options about GBS vaccine and clinical trials are also self-reported. Most of our participants self-identified as white with high levels of education, limiting the generalizability of our findings. This limitation highlights the challenges of recruiting a cohort of participants that are representative of the general population.

CONCLUSIONS

Participants in our study expressed a good understanding of GBS. There is mixed acceptability for participation in a novel GBS vaccine clinical trial during pregnancy with a greater acceptability during lactation. Knowledge of GBS and experience with GBS are associated with greater willingness to participate in novel GBS vaccine trials. Further studies on GBS vaccine in pregnancy are needed, and specifically studies with participants that represent the general population. The perspectives of pregnant and lactating people are critical to appreciate as new vaccines are being developed.