Immunological Correlates of Protection Induced by a Next-Generation Nasal Mucosal Vaccine Against Respiratory Syncytial Virus (RSV) in Older Adults
Research Paper | 2026 | Volume 1 | Issue 01 | Page 57-61
Dr. Srinathan Ramayea, Assistant Professor Department of Respiratory Medicine, Under Dr. MGR Medical University, TN
ABSTRACT
BACKGROUND: Respiratory Syncytial Virus (RSV) poses a significant burden of morbidity and mortality in the elderly population, where immunosenescence often renders traditional intramuscular vaccines less effective. Nasal mucosal vaccines, by inducing local secretory IgA and tissue-resident memory T cells (Trm), may provide superior protection at the site of viral entry. This study aimed to characterize the immunological correlates of protection (CoP) induced by a novel intranasal mucosal vaccine in older adults.
METHODS: In this Phase I/II clinical trial, 80 healthy adults aged 65–80 years were randomized to receive either the intranasal mucosal vaccine or a placebo. Systemic and mucosal immune responses were monitored at baseline, 28 days, and 6 months post-vaccination. Primary endpoints included the induction of RSV-specific secretory IgA (sIgA) in nasal secretions, systemic RSV-F protein-specific IgG titers in serum, and the frequency of RSV-specific CD4+ and CD8+ T cells in peripheral blood mononuclear cells (PBMCs) and nasal epithelial brushings. RESULTS: The intranasal vaccine was well-tolerated and elicited a robust, durable mucosal immune response. Participants receiving the vaccine showed a significant increase in RSV-specific sIgA levels in nasal secretions, peaking at 28 days (p < 0.001) and remaining detectable at 6 months. Concurrently, a significant expansion of RSV-specific tissue-resident memory CD8+ T cells (CD69+CD103+) was observed in the nasal mucosa. Systemic IgG responses were detected but were lower in magnitude compared to mucosal IgA. Modeling identified mucosal sIgA titers as the primary correlate of protection against experimental viral challenge in a subset analysis.
CONCLUSION: Intranasal vaccination effectively overcomes immunosenescence in older adults by priming the mucosal immune system. The induction of durable local sIgA and Trm cell populations in the nasal cavity represents a critical correlate of protection that may provide enhanced immunity against RSV compared to systemic approaches. These findings support the continued development of mucosal delivery platforms for RSV prevention in the elderly.
KEYWORDS: RSV, Mucosal Vaccine, Older Adults, Immunosenescence, Secretory IgA, Tissue-Resident Memory T Cells, Correlates of Protection.
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