Sex Differences in Response to Viral Vector Vaccines—Implications for Future Vaccine Design

Vaccination represents one of the most impactful public health achievements, preventing 3.5 to 5 million deaths annually according to estimates of the World Health Organization. Yet, recent outbreaks of emerging and reemerging infectious diseases highlight the need for rapid and strategic vaccine development using vaccine platforms technologies. Sexual dimorphism in vaccine-induced immune responses has received significant attention in recent years. To ensure vaccine safety and efficacy across sexes, sex-based differences should be considered in vaccine design, dosing, and regimen. Evidence on many traditional vaccines, such as the inactivated influenza vaccine, shows a female bias in innate and adaptive immune responses following vaccination. Thus, it has long been suggested that females universally develop stronger humoral and cellular immune responses to vaccines compared to males. However, compared to traditional vaccines, studies investigating sex differences following vaccination with next-generation platforms, such as viral vector vaccines, remain limited. This review provides an overview of clinical observations of sex differences in responses to replication-competent and replication-deficient, recombinant and nonrecombinant viral vaccines. Additionally, we describe the current state of knowledge on mechanisms of sex-based differences in immune responses and possible implications for future vaccine design.