Vaccines Against Hantavirus Infections: A Systematic Literature Review

Background/Objectives: Hantaviruses infections are responsible for a hemorrhagic fever with renal and cardiopulmonary syndrome with case-fatality rates up to 50%. While inactivated vaccines are already available in China and South Korea, several additional candidate vaccines are under development. This systematic review summarizes the current clinical evidence on immunogenicity and short-term safety of vaccines targeting different hantavirus strains. Methods: Following PRISMA 2020 guidelines, a systematic literature search was carried out to identify randomized and nonrandomized trials of any phase. Data were synthesized narratively within strata defined by vaccine platform, target virus, assay, immunogenicity and safety. Results: Ten trials on 961 adults were included: four single-arm trials on the inactivated vaccine and six early-phase DNA-vaccine trials. One month after last dose, the inactivated vaccine achieved neutralizing seropositivity by PRNT₅₀ in 45.1% of the tested subjects after two priming doses and 55.7% after three, while the corresponding binding-antibody values measured by IFA were 87.3% and 95.7%. Among DNA vaccines, homologous responses reached 100% against HTNV and 83.3% against PUUV with monovalent constructs, whereas dual responses to the bivalent construct were registered in 33.3% and 77.8% of the subjects, when measured through PRNT₅₀ and PsVNA₅₀, respectively. One serious adverse event occurred, most likely unrelated to vaccination. Conclusions: No serious safety signal was identified, although safety remains insufficiently characterized. Measured immunogenicity depends as much on the assay as on the vaccine, and, in the absence of a validated correlate of protection, it cannot be read as a clinical benefit. Future research should prioritize validated correlates of protection and innovative trial designs adapted to low-incidence diseases.