The mRNA-1345 RSV vaccine demonstrated enhanced humoral immunogenicity in older adults, with significant increases in neutralizing antibodies (nAbs) and preF-binding antibodies (bAbs) against both RSV-A and RSV-B subtypes. In a phase 2/3 trial, participants aged ≥60 years received either mRNA-1345 (50 µg) or placebo. At day 29 post-vaccination, nAb geometric mean titers (GMTs) increased 8.4-fold against RSV-A and 5.1-fold against RSV-B. Seroresponse rates were 74.2% for RSV-A and 56.5% for RSV-B. PreF bAbs also increased, with patterns similar to nAbs. Immunogenicity results were consistent across demographic and risk subgroups, including those at higher risk for severe RSV disease. The vaccine showed durable immune responses, with GMTs remaining elevated at day 29 and consistent with overall trial results. The findings support the vaccine's efficacy in preventing RSV disease in older adults, with strong immune responses observed in both RSV-A and RSV-B subtypes. The study highlights the importance of mRNA-1345 as a promising vaccine candidate for RSV prevention in high-risk populations.The mRNA-1345 RSV vaccine demonstrated enhanced humoral immunogenicity in older adults, with significant increases in neutralizing antibodies (nAbs) and preF-binding antibodies (bAbs) against both RSV-A and RSV-B subtypes. In a phase 2/3 trial, participants aged ≥60 years received either mRNA-1345 (50 µg) or placebo. At day 29 post-vaccination, nAb geometric mean titers (GMTs) increased 8.4-fold against RSV-A and 5.1-fold against RSV-B. Seroresponse rates were 74.2% for RSV-A and 56.5% for RSV-B. PreF bAbs also increased, with patterns similar to nAbs. Immunogenicity results were consistent across demographic and risk subgroups, including those at higher risk for severe RSV disease. The vaccine showed durable immune responses, with GMTs remaining elevated at day 29 and consistent with overall trial results. The findings support the vaccine's efficacy in preventing RSV disease in older adults, with strong immune responses observed in both RSV-A and RSV-B subtypes. The study highlights the importance of mRNA-1345 as a promising vaccine candidate for RSV prevention in high-risk populations.