Industry Insights: Multiomics, mucosal immunity, and mRNA vaccine benefits
Vaccine Insights 2025; 4(9), 383–387
DOI: 10.18609/vac.2025.053
 | DISCOVERY AND IMMUNOLOGY |
Multiomics reveals molecular mechanisms behind weakened vaccine responses in older adults [1]Gong Q, Sharma M, Glass MC, et al. Multi-omic profiling reveals age-related immune dynamics in healthy adults. Nature 2025; published online Oct 29.
Tracking 96 healthy young and older adults over 2 years, researchers at the Allen Institute used single-cell RNA sequencing, proteomics, and spectral flow cytometry to show that specific, nonlinear age-related changes in T cells contribute to weaker vaccine responses in older adults. These findings were supported by the Human Immune Health Atlas, mapping 71 immune cell types and over 16 million cells from adults aged 25 to 90+.
 | FORMULATION AND DELIVERY |
Novel LNP with 100-fold lower dose of influenza mRNA vaccine in mice [2]Rudra A, Gupta A, Reed K, et al. Degradable cyclic amino alcohol ionizable lipids as vectors for potent influenza mRNA vaccines. Nat. Nanotechnol. 2025; published online Nov 7.
MIT scientists reported that a new LNP platform, based on degradable cyclic amino ionizable lipids, enabled dosing of an mRNA influenza vaccine at a 100-fold lower dose than a conventional ionizable lipid.
Intranasal pertussis vaccine generates strong local T cell immunity in mice [3]Jazayeri SD, Borkner L, Sutton CE, Mills KHG. Respiratory immunization using antibiotic-inactivated Bordetella pertussis confers T cell-mediated protection against nasal infection in mice. Nat. Microbiol. 2025; published online Nov 10.
Researchers at Trinity College Dublin reported preclinical results for a novel intranasal pertussis vaccine formulated using antibiotic-inactivated Bordetella pertussis [3]Jazayeri SD, Borkner L, Sutton CE, Mills KHG. Respiratory immunization using antibiotic-inactivated Bordetella pertussis confers T cell-mediated protection against nasal infection in mice. Nat. Microbiol. 2025; published online Nov 10. . In mice, administration of the vaccine via aerosol or intranasal routes conferred a high level of protection, outperforming both current acellular and historic whole-cell vaccines.
Intranasal recombinant H5N1 vaccine induces mucosal and systemic immunity in adults [4]Deming ME, Toapanta FR, Pasetti M, et al. An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades: a phase I trial. Nat. Commun. 2025; published online Nov 6.
A Phase 1 randomized, placebo-controlled trial evaluated NanoVax’s intranasal recombinant H5N1 influenza vaccine in 40 adults aged 18–45 years. Participants received low, medium, or high doses of the adjuvanted clade 2.1 rH5 vaccine, an unadjuvanted dose, or placebo, followed by an intramuscular H5 booster 6 months later. The adjuvanted intranasal vaccine elicited higher IgG and IgA antibody levels, increased memory immune cells, and improved neutralizing activity compared with unadjuvanted or placebo groups.
5-methylcytidine modulates innate immunity in self-amplifying RNA vaccines [5]Akahata W, Komori M, Morey AL, et al. Incorporation of 5-methylcytidine alleviates RIG-I-mediated innate immune responses to a self-amplifying RNA vaccine. Sci. Transl. Med. 2025; published online Nov 12.
VLP Therapeutics, Boston University, and NIH researchers reported that incorporating modified base 5-methylcytidine (5mC) into replicon-based saRNA COVID-19 vaccines reduced excessive innate immune activation via suppressing type I interferon production by plasmacytoid dendritic cells, while maintaining strong adaptive responses.
 | CLINICAL TRIALS |
IAVI’s rVSVΔG-LASV-GPC Lassa vaccine safe and immunogenic in Phase 1 trial [6]Malkin E, Zaric M, Kieh M, et al. Safety and immunogenicity of an RSV Lassa Fever vaccine candidate. N. Engl. J. Med. 2025; published online Nov 5;
A first-in-human Phase 1 trial of IAVI’s rVSV vector-based Lassa virus vaccine candidate demonstrated an acceptable safety profile and robust, durable immune responses after a single dose. The study enrolled 114 adults in the US and Liberia, who received one of four dose levels or placebo and were followed for 12 months. Humoral and cellular responses were robust across all dose levels, with antibodies cross-reactive to multiple Lassa virus lineages. No vaccine-related serious adverse events were observed.
Better protection but more reactogenicity in Phase 3 trial of Moderna’s mRNA influenza vaccine [7]Fitz-Patrick D, McVinnie DS, Jackson LA, et al. Efficacy, immunogenicity, and safety of modified mRNA influenza vaccine. N. Engl. J. Med. 2025; published online Nov 19.
A randomized trial of more than 18,000 adults aged 18–64 years compared a modified mRNA influenza vaccine with a licensed inactivated vaccine during the 2022–2023 season. The mRNA vaccine reduced laboratory-confirmed influenza by 60–67%, versus 44–54% for the traditional vaccine. However, local and systemic reactions were more frequent. Serious adverse events were rare and comparable between groups, with no myocarditis cases observed at 6 months follow up.
Greater risk of cardiac complications in children after COVID-19 infection than vaccination [8]Sampri A, Shi W, Bolton T, et al. Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records. Lancet Child Adolesc. Health 2025; 9, 837–847.
A retrospective cohort study of nearly 14 million children aged under 18 in England assessed short- and long-term risks of rare cardiovascular and inflammatory complications following COVID-19 infection or BNT162b2 vaccination. Over 6 months, infection was associated with 2.24 additional myocarditis or pericarditis cases per 100,000, compared with 0.85 after vaccination.
RTS,S/AS01E malaria vaccine maintains effectiveness in real-world use [9]Ndeketa L, Haine V, Debois M, et al. Effectiveness of the RTS,S/AS01(E) malaria vaccine in a real-world setting over 1 year of follow-up after the three-dose primary schedule: an interim analysis of a phase 4 study in Ghana, Kenya, and Malawi. Lancet Glob. Health 2025; published online Nov 6.
A Phase 4 surveillance study across Ghana, Malawi, and Kenya found that the RTS,S/AS01E malaria vaccine demonstrated real-world effectiveness consistent with clinical trial results. Researchers followed 45,000 children under 5 for 1 year after completion of the three-dose primary schedule. Adjusted incidence rate ratios showed a 30% reduction in malaria and a 58% reduction in severe malaria among vaccinated children.
New human challenge models for hMPV, RSV B, and SARS-CoV-2 Omicron BA.5 [10]
hVIVO reported data from several newly developed human challenge models at the World Vaccine Congress Europe. The company presented findings from its contemporary-strain hMPV model, its SARS-CoV-2 Omicron BA.5 model, and its first RSV B challenge model.
 | THERAPEUTIC VACCINES |
COVID-19 mRNA vaccination linked to longer survival in cancer immunotherapy patients [11]Grippin AJ, Marconi C, Copling S, et al. SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade. Nature 2025; 647, 488–497.
In a retrospective analysis, researchers from the University of Florida and the University of Texas MD Anderson Cancer Center reported that receiving a COVID-19 mRNA vaccine within 100 days of initiating immune checkpoint inhibitor therapy for advanced non-small cell lung cancer or metastatic melanoma was associated with significantly improved survival. The researchers hope to confirm the findings in a prospective, randomized trial.
Intranasal nanogel HPV vaccine shows therapeutic activity against cervical cancer in preclinical models [12]Nakahashi-Ouchida R, Mori H, et al. Cationic nanogel-based nasal therapeutic HPV vaccine prevents the development of cervical cancer. Sci. Transl. Med. 2025; published online Nov 12.
Researchers at Chiba University developed a cationic nanogel–based intranasal therapeutic vaccine targeting the HPV16 E7 oncoprotein and demonstrated antitumor activity in mice and macaques. In mice, intranasal vaccination slowed tumor growth and induced strong E7-specific CD4+ and CD8+ T cell responses in cervicovaginal tissue. In macaques, four intranasal doses administered via a human-compatible spray device elicited robust and sustained cervical mucosal immunity, including persistent E7-specific cytotoxic T cells.
 | MANUFACTURING INNOVATION |
CSL Seqirus supports local production of cell-based influenza vaccines in Saudi Arabia [13]
CSL Seqirus entered a collaboration with the Saudi Ministry of Health to supply seasonal and pandemic cell-based influenza vaccines and to support the establishment of local manufacturing capacity. Working with Vaccine Industrial Company, Seqirus will help set up production at a facility in Sudair City and assist in building pre-pandemic vaccine stockpiles for high-risk groups, alongside an advance purchase agreement for broader pandemic immunization.
 | MARKET TRENDS |
Moderna secures $1.5B loan and outlines strategy amid declining vaccine revenue [14]
Moderna announced it has obtained a $1.5 billion, 5-year loan facility from Ares Management Credit Funds as it restructures its pipeline and aims to break even by 2028. The company reported continued revenue declines in a post-pandemic market after limited market uptake of its RSV vaccine and disappointing clinical trial results for its CMV program. The company’s 3-year strategy targets up to 10% revenue growth in 2026, driven by upcoming seasonal vaccines for norovirus, influenza, and a combined flu/COVID candidate.
References
1. Gong Q, Sharma M, Glass MC, et al. Multi-omic profiling reveals age-related immune dynamics in healthy adults. Nature 2025; published online Oct 29. Link
2. Rudra A, Gupta A, Reed K, et al. Degradable cyclic amino alcohol ionizable lipids as vectors for potent influenza mRNA vaccines. Nat. Nanotechnol. 2025; published online Nov 7. Link
3. Jazayeri SD, Borkner L, Sutton CE, Mills KHG. Respiratory immunization using antibiotic-inactivated Bordetella pertussis confers T cell-mediated protection against nasal infection in mice. Nat. Microbiol. 2025; published online Nov 10. Link
4. Deming ME, Toapanta FR, Pasetti M, et al. An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades: a phase I trial. Nat. Commun. 2025; published online Nov 6. Link
5. Akahata W, Komori M, Morey AL, et al. Incorporation of 5-methylcytidine alleviates RIG-I-mediated innate immune responses to a self-amplifying RNA vaccine. Sci. Transl. Med. 2025; published online Nov 12. Link
6. Malkin E, Zaric M, Kieh M, et al. Safety and immunogenicity of an RSV Lassa Fever vaccine candidate. N. Engl. J. Med. 2025; published online Nov 5; Link
7. Fitz-Patrick D, McVinnie DS, Jackson LA, et al. Efficacy, immunogenicity, and safety of modified mRNA influenza vaccine. N. Engl. J. Med. 2025; published online Nov 19. Link
8. Sampri A, Shi W, Bolton T, et al. Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records. Lancet Child Adolesc. Health 2025; 9, 837–847. Crossref
9. Ndeketa L, Haine V, Debois M, et al. Effectiveness of the RTS,S/AS01(E) malaria vaccine in a real-world setting over 1 year of follow-up after the three-dose primary schedule: an interim analysis of a phase 4 study in Ghana, Kenya, and Malawi. Lancet Glob. Health 2025; published online Nov 6. Link
10. Financial Times. Positive data from multiple novel human challenge models. Nov 1, 2025.
11. Grippin AJ, Marconi C, Copling S, et al. SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade. Nature 2025; 647, 488–497. Crossref
12. Nakahashi-Ouchida R, Mori H, et al. Cationic nanogel-based nasal therapeutic HPV vaccine prevents the development of cervical cancer. Sci. Transl. Med. 2025; published online Nov 12. Link
13. CSL Seqirus. CSL Seqirus and Vaccine Industrial Company sign landmark Memorandum of Understanding with Ministry of Health to localize manufacturing of cell-based seasonal and pandemic influenza vaccines. Oct 30, 2025.
14. Moderna. Moderna secures $1.5 billion five-year credit facility from Ares Management. Nov 20, 2025.