Next-generation mucosal vaccines for respiratory viruses: Immunological correlates, platform design and clinical translation

Table 1 Comparison of mucosal vaccine platforms

Platform	Example	Route	Mechanism/design	Noted immune features	Advantages	Key limitations	Status
LAIV[38]	FluMist® (MedImmune/AstraZeneca)	Intranasal spray	Cold-adapted live attenuated influenza virus replicates in nasal mucosa	Induces mucosal immunity; long track record in children	Licensed product; needle-free	Contraindicated in some groups; live virus	FDA-licensed; self/caregiver administration cleared September 20, 2024, with consumer rollout for 2025-2026 season
Adenoviral vector (inhaled)[39]	Convidecia Air™ (CanSinoBIO)	Inhaled aerosol	Ad5 vector; aerosolized booster formulation	Authorization news; peer-reviewed human mucosal immunogenicity not detailed in approval notice)	First approved inhaled COVID-19 booster; needle-free	Vector immunity; limited published efficacy data	Emergency use authorized in China (September 2022)
Adenoviral vector (intranasal)[40]	iNCOVACC™ (Bharat Biotech)	Intranasal spray	Non-replicating Ad5 vector expressing SARS-CoV-2 spike	Reported immunogenicity in Phase III; used as primary series or heterologous booster in India	Needle-free; deployable as booster	Vector immunity; comparative efficacy vs IM still being studied	India approval for primary 2-dose series and heterologous booster (restricted emergency use)
Live attenuated influenza-vectored[41]	dNS1-RBD (Beijing Wantai; “Pneucolin”)	Intranasal spray	ΔNS1 influenza backbone expressing SARS-CoV-2 RBD	Phase 3 overall VE 28.2% against symptomatic Omicron; safety acceptable	True mucosal delivery; some infection reduction	Modest efficacy in Omicron period	Phase 3 RCT completed; results published
Protein subunit + mucosal adjuvant[42]	Intranasal multivalent H5 (UMD/BlueWillow; nanoemulsion adjuvant)	Intranasal spray	Recombinant H5 antigen(s) + nanoemulsion (NanoVax® W805EC)	Phase 1 broad immune response incl. mucosal; strong priming	Stockpile-friendly concept; non-live	Needs adjuvant; data early-phase	Phase 1 RCT results published (nature communications, 2025) and institutional news

RCT: Randomized controlled trial; LAIV: Live attenuated influenza vaccine; Ad5: Adenovirus serotype 5; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; RBD: Receptor-binding domain; VE: Vaccine efficacy; IM: Intramuscular; FDA: United StatesFood and Drug Administration; ΔNS1: Deletion of nonstructural protein 1; H5: Influenza A(H5) hemagglutinin subtype.