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

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.