The battle against RSV: Infants and children in the front line!

Abstract

Background: In the past year, respiratory syncytial virus (RSV) vaccine development has received increased attention, particularly after several clinical trials involving infants and children were stopped because of safety concerns. These events have raised scientific and ethical questions, especially when compared to a similar historical case. In the 1960s, clinical trials of the formalin-inactivated RSV vaccine Lot-100 were also stopped after many vaccinated infants and children became severely ill, and two died.

Objective: This ethical analysis examines the clinical trials related to RSV vaccine Lot-100 development conducted in the 1960s to identify lessons from a research ethics perspective. These lessons can inform current vaccine research involving vulnerable populations such as infants and children.

Methods: A systematic literature search was conducted across PubMed, Embase, and Google Scholar in accordance with PRISMA guidelines. Information about the trials was extracted and organized using a structured framework with predefined categories. The trials were then evaluated using the ethical principles for clinical research developed by Emanuel, Wendler, and Grady (2000).

Results: 18 studies met the inclusion criteria, including four reports of clinical trials in infants and children for the development of the RSV vaccine Lot-100 conducted in the 1960s. The reports of the four clinical trials were used for ethical evaluation because the other included studies lacked sufficient detail. These four RSV clinical trials varied in design, setting and study population. All four trial reports documented that vaccinated infants and children experienced more severe illness following natural RSV infection compared to control groups. Two deaths were reported in one of the trials. The review highlights ethical concerns related to fair subject selection, favorable risk-benefit ratio and informed consent. Ethical concerns included limited reporting of inclusion and exclusion criteria, absent documentation of informed consent in half of the trials. Vulnerable populations such as institutionalized, ethnically or socioeconomically disadvantaged children were enrolled. Frequent and sometimes invasive sampling procedures were conducted across all trials.

Conclusion: The Lot-100 clinical trials were of relatively good scientific quality given the standards of the 1960s. However, ethical evaluation reveals several important lessons. Trials involving vulnerable populations, such as infants and children, must be based on strong scientific justification, apply fair subject selection, and ensure a favorable risk-benefit ratio with attention to potential unknown risks. Transparent and well-documented informed consent procedures are essential. These ethical lessons remain highly relevant for current and future vaccine research involving vulnerable populations, such as infants and children. Furthermore, public communication about research outcomes must be objective, transparent and with careful attention to nuance to avoid undermining trust in vaccination efforts.