Moderna (Nasdaq: MRNA) has registered a Phase I study of mRNA-1365 (Profile 2), a bivalent mRNA vaccine targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), in adults aged 60 and older. The study brings the RSV/hMPV combination back into clinical development after an earlier pediatric program involving mRNA-1365 was placed on clinical hold following severe RSV infections in vaccinated infants.
The randomized, open-label, staggered dose-escalation study (NCT07764237) plans to enroll 375 participants across Canada and the United Kingdom. Three dose levels of mRNA-1365 (Profile 2) will be evaluated alongside two formulations of mRNA-1345, Moderna's RSV vaccine, as active comparators. The trial started August 11, 2026, according to the registry, with primary completion expected in July 2027. Immunogenicity endpoints include RSV and hMPV neutralizing antibody titers and seroresponse rates at Day 29.
The adult program follows a safety setback in RSV-naive infants in 2024. Moderna paused dosing in a pediatric Phase I study of mRNA-1345 and mRNA-1365 in July that year after severe RSV lower respiratory tract infections occurred more frequently among vaccine recipients than placebo, prompting US FDA clinical holds and concerns about possible vaccine-associated enhanced respiratory disease. Five of 35 vaccine recipients experienced severe or hospitalized RSV infections, compared with one of 18 placebo recipients.
The US FDA's Vaccines and Related Biological Products Advisory Committee reviewed the findings in December 2024 and recommended caution in further development of RSV vaccines in RSV-naive infants. The new mRNA-1365 study instead targets adults aged at least 60, a population with previous natural exposure to RSV, and excludes participants who have received a licensed RSV vaccine or previously participated in an RSV or hMPV vaccine study.
mRNA-1365 combines antigens targeting RSV and hMPV, two respiratory viruses associated with lower respiratory tract disease in older adults. The RSV component targets the prefusion F protein also used by Moderna's approved RSV vaccine mRESVIA, while the hMPV component targets the virus's F protein. No hMPV vaccine is currently approved.