Rubella and Zika Vaccine Research—A Cautionary Tale About Caution

Abstract

The public health response to the Zika crisis has evoked debate and critique, although there has been at least 1 clear success: rapid progress toward a vaccine, with phase 2 testing starting in early 2017, just a year after the Public Health Emergency of International Concern was declared. Among the challenges of developing a vaccine to prevent Zika infection during pregnancy are ethically complex questions about the appropriate role of pregnant women in the vaccine development agenda. Though ideally women will be vaccinated before conceiving, inadvertent vaccination during pregnancy is unavoidable when women of childbearing age are targeted. Vaccination during pregnancy may also be beneficial because the risks of Zika infection persist through gestation. 1 Both underscore the importance of developing an approach that meets the needs of those most at risk: pregnant women and their offspring.To some extent, the timing is auspicious. Vaccination during pregnancy is increasingly accepted and endorsed-the Advisory Committee for Immunization Practices recommends pertussis and inactivated influenza vaccines for all pregnant women. However, certain vaccines are contraindicated-notably, live attenuated vaccines such as measles, mumps, and

Pregnant women's perceptions of risks and benefits when considering participation in vaccine trials

“…Similarly, physiologic alterations in immune function can potentially impact immune response to vaccines [21] . Historically, vaccine development has established safety in non-pregnant populations then proceeds to market and clinical use, without plans to establish safety or efficacy in pregnancy, despite likely benefit and certain inadvertent exposure [21] , [28] . Further, the working interpretation of FDA approval for use in adult populations is that the approval extends to healthy pregnant women, despite potential differences in safety and efficacy [20] .…”

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

“…However, as discussed in Recommendation 1 , many things can go wrong over the course of pregnancy into early infancy, and some may be inappropriately attributed to the vaccine. The mishandling of risk communication of suspected pregnancy-specific adverse events during an outbreak or epidemic can lead to significant harms to pregnant women and their offspring, including women choosing to forego use of beneficial vaccines or unnecessarily seeking to terminate wanted pregnancies [74] ( see Box 4 ). Therefore, a critical best practice for communicating pregnancy-specific vaccine findings is to ensure that any reports of adverse pregnancy or birth outcomes occurring during the epidemic response are interpreted in light of the best available information about baseline rates of adverse obstetric and neonatal events, and should include an acknowledgement that a high percentage of adverse events in pregnancy have no known cause.…”

Serologic Tools and Strategies to Support Intervention Trials to Combat Zika Virus Infection and Disease

“…Because CZS is the major public health problem caused by ZIKV infection, it is vital to consider the involvement of pregnant women in ZIKV intervention trials. With influenza infection being an exception, there is very little literature on Ab-mediated immunity to emerging infectious diseases in pregnant compared to non-pregnant women [192], one reason being that pregnant women are often systematically excluded from research studies [193]. A recent non-human primate study of pregnant versus non-pregnant female macaques suggested no differences, but more work will be required to assure that we understand the effect of the pregnant state on serologic responses ZIKV and whether potential differences affect the performance of serodiagnostic tests.…”