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.

Table 2 Recent clinical readouts for intranasal/inhaled respiratory vaccines (2022-2025)

Pathogen	Candidate and developer	Platform/route	Phase/setting	Key immune or clinical finding	Outcome/status
SARS-CoV-2[68]	ChAdOx1 nCoV-19 (Oxford/AZ) intranasal	Chimp adenoviral vector; intranasal	Phase 1, United Kingdom	Mucosal antibody responses detected in a minority; systemic responses weaker than IM; no safety concerns	Program not advanced further based on weak mucosal/systemic responses
SARS-CoV-2[41]	dNS1-RBD (“Pneucolin”, Wantai)	Live attenuated influenza vector; intranasal	Phase 3, multi-country, Omicron period	Overall VE 28.2% (95%CI: 3.4-46.6) against symptomatic infection (1.6% vaccine vs 2.3% placebo); acceptable safety	Demonstrated modest efficacy; first large RCT efficacy signal for an intranasal COVID-19 vaccine
SARS-CoV-2[39]	Convidecia Air™ (CanSinoBIO)	Ad5 vector; inhaled aerosol	Post-approval booster use (China)	Approved for booster use; first inhaled COVID-19 vaccine authorized	Emergency use authorization granted September 2022 (China NMPA)
SARS-CoV-2[40]	iNCOVACC™ (Bharat Biotech)	Ad5 vector; intranasal	India approvals	Approved for primary series and heterologous booster; phase III immunogenicity conducted in about 3100 subjects	Restricted emergency use authorization in India
Influenza A(H5)[38]	Intranasal H5 nanoemulsion-adjuvanted vaccine (UMD/BlueWillow)	Protein subunit + nanoemulsion; intranasal	Phase 1, United States adults	Broad immune response across H5 clades; robust priming for later IM boost (as reported)	Phase 1 RCT results published (nature communications, 2025)
RSV[69]	BLB201 (Blue Lake Biotechnology)	PIV5 vector; intranasal	Phase 1/2a (adults; pediatric expansion)	Interim reports: Immunogenicity and tolerability in adults; pediatric seropositive cohort showed mucosal/serologic responses (company communications)	Early-phase development; interim data communicated by sponsor

COVID-19: Coronavirus disease 2019; RSV: Respiratory syncytial virus; IM: Intramuscular; VE: Vaccine efficacy; RCT: Randomized controlled trial; NMPA: National Medical Products Administration (China); Ad5: Adenovirus serotype 5; PIV5: Parainfluenza virus type 5; RSV: Respiratory syncytial virus.

Table 3 Regulatory and deployment updates relevant to mucosal vaccines

Item	Jurisdiction	Detail
First inhaled COVID-19 booster approval[39]	China	Convidecia Air™ (Ad5 aerosol) received emergency authorization as a booster (September 2022)
First intranasal COVID-19 vaccine approval[40]	India	iNCOVACC™ approved for primary series and heterologous booster under restricted emergency use
LAIV self-administration pathway[38]	United States (FDA)	FluMist® approved for self/caregiver administration (September 20, 2024); broad home-use rollout for 2025-26 season

COVID 19: Coronavirus disease 2019; LAIV: Live attenuated influenza vaccine; Ad5: Adenovirus serotype 5; FDA: United States Food and Drug Administration.