Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response

Abstract

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders.

A new twenty-first century science for effective epidemic response

“…In 2016, the PREVENT project received Wellcome funding to provide ethics guidance "at the intersection of pregnancy, vaccines, and emerging and re-emerging epidemic threats" 93 . This was in response to the newly recognized association between infection with Zika virus during pregnancy and microcephaly in the newborn.…”

Pregnancy Outcomes among Women Receiving rVSVΔ-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola

“…The World Health Organization's Strategic Advisory Group of Experts on Immunization, recognizing the high risk for maternal and fetal death from Ebola virus infection, has endorsed the need for careful evaluation of risks and benefits in a local context by national regulatory authorities and ethics committees in decisionmaking about rVSVΔG-ZEBOV-GP vaccination of pregnant women during an Ebola outbreak (27). The decision to offer rVSVΔG-ZEBOV-GP vaccine to pregnant women will need to balance the risk for an adverse pregnancy outcome with the risk for exposure to and subsequent infection with Ebola (28)(29)(30)(31)(32)(33). When vaccination is offered to pregnant women, the provision of culturally appropriate information to assist women in making informed decisions about whether to accept vaccination will be critical.…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…156 Conventional vaccination has been an approach targeted at all groups and individuals but has failed toward the enrolment of pregnant women into vaccination programs because of presumed fetal and maternal harms. 157,158 Evidence on the safety of vaccination in pregnancy is very small because pregnant women were usually excluded from participating in vaccine trials. 159 Pregnancy can alter the maternal as well as fetal immunological responses.…”

“…160 It is pertinent to explore research opportunities presented in advanced vaccine designs such as immunoinformatics (multiepitope vaccine docking) by studying human immune system functions and responses specific to pregnant women and their unborn children. 157 According to a report 161 from the Dominican Republic of Congo, during the 2016-2017 Zika virus outbreaks, over a thousand pregnant women were suspected of being infected with the virus and a sizable number were at their first trimester. The report further stated that fetal loss was approximately one-tenth of the pregnancies and that there were up to 3 cases of fetus with head circumferences smaller than normal.…”

“…162 Designing, implementing and enrolling pregnant women as well as perspective pregnant women into vaccine trials and programs is imperative in order to protect this group and ensure good vaccine uptake by them during infection outbreaks and epidemics. 157,163 These recommendations will give an informed decision to be investigated using the immunoinformatic tools to determine the immunogenic responses worthy of safe vaccine development for the pregnant women and perspective pregnant women group.…”