Jul 2026· Journal of Immunology· Vol 215· 0 citations
TL;DR
It is demonstrated that antigenic clade-matching is likely critical for protection against H5N1 and suggest that currently stockpiled H5N1 vaccines may not protect against contemporary viruses.
Abstract
Highly pathogenic avian influenza viruses (HPAIs) continue to threaten both agriculture and human health. Recent H5N1 clades have caused zoonotic infections in humans with mortality rates approaching 50%. However, currently licensed H5 vaccines are based on ancestral strains and may provide suboptimal protection against circulating variants. Rapidly adaptable DNA vaccine platforms offer a promising approach for clade-specific protection.
Codon-optimized plasmid DNA vaccines expressing hemagglutinin (HA) from two recently circulating H5N1 clades (2.3.2.1c and 2.3.4.4b) were generated and delivered by either intramuscular electroporation (EP) or a lipid nanoparticle (LNP) formulation. Cellular and humoral responses were evaluated by multiparameter flow cytometry and ELISpot and by ELISA and pseudovirus neutralization, respectively. Protective efficacy was evaluated in lethal H5N1 murine challenge models.
EP delivery of clade 2.3.2.1c HA (pCamb) elicited strong humoral and cellular responses and achieved complete protection against homologous viral challenge, but only partial protection against heterologous 2.3.4.4b challenge. In contrast, vaccination with clade 2.3.4.4b HA (pMich) DNA supported robust immune responses and full protection against contemporary clade challenge. Co-immunization with both plasmids via EP induced broad binding and neutralizing antibodies and conferred complete protection from clade 2.3.4.4b challenge. Moreover, formulation of the pMich plasmid optimized LNPs generated durable, protective immunity following a single dose, effective at both acute and memory timepoints.
These studies demonstrate that antigenic clade-matching is likely critical for protection against H5N1 and suggest that currently stockpiled H5N1 vaccines may not protect against contemporary viruses. Further this data suggests that DNA vaccine platforms including EP or LNP formulations can provide a flexible approach for rapid adaptation to evolving influenza strains.
NIH NIAID CIVICs
Vaccines and Immunotherapy (VAC)
A bivalent chimeric inactivated vaccine, designated cHANA, is developed by combining two individually rescued chimeric inactivated viruses, cHANA1 and cHANA2, by combining two individually rescued chimeric inactivated viruses to eliciting more potent cross-reactive antibody responses and T cell immunity in mice.
Mengchan Hao, Yiwei Guan, Meng Xu et al.· Emerging Microbes and Infect...· 0 citations
Orthoebolaviruses, including Zaire virus, Sudan virus, and Bundibugyo virus, remain major public health threats because of their high case-fatality rates and recurrent outbreaks. Although licensed vaccines provide effective protection against EBOV, broadly protective vaccines against multiple pathogenic orthoebolavirus species remain unavailable. Here, we developed T4 bacteriophage-based nanoparticle vaccines displaying glycoproteins (GPs) from EBOV, SUDV, and BDBV by leveraging the SpyTag/SpyCatcher conjugation system. Monovalent vaccine candidates and a trivalent formulation (T4-Mix) were generated to evaluate their potential for broad orthoebolavirus immunization. Intramuscular immunization of BALB/c mice elicited robust GP-specific humoral and cellular immune responses without the need for exogenous adjuvants. In homologous surrogate challenge models using replication-competent recombinant vesicular stomatitis viruses expressing EBOV, SUDV, or BDBV GP, all monovalent vaccines conferred complete protection against their respective challenge viruses. Furthermore, the optimized trivalent T4-Mix formulation provided complete protection against rVSV-EBOV, rVSV-SUDV, and rVSV-BDBV challenges. Collectively, these findings demonstrate that the T4 bacteriophage functions as both an antigen delivery vehicle and an intrinsic immunostimulatory scaffold, highlighting its potential as a versatile platform for the development of broadly protective multivalent orthoebolavirus vaccines.
Jun-Hui Zhou, Xing-Hai Zhang, Xin-Feng Li et al.· Antiviral Research· 0 citations
Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90 days after receiving two intramuscular doses of the H5N8 vaccine (15 μg HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.
D. Maria, Isabela Mancini Martins, Giselle Pidde Marques Porto et al.· Vaccine· 0 citations
The findings suggest that internal gene backbone compatibility may influence vaccine immunogenicity and warrant further validation to support a refined vaccine design strategy for H7N9 and potentially other avian influenza subtypes.
Yi Liu, Meng-Yuan Bai, Tao Zhang et al.· Microorganisms· 0 citations
The two proposed multi-epitope mRNA vaccine constructs showed promising immunogenic, safety, and structural properties in silico, highlighting their potential as candidate vaccines against HMPV.
E. K. Oladipo, James Akinwumi Ogunniran, Oluwaseyi Samuel Akinpelu et al.· Discover Immunity· 0 citations
INTRODUCTION
Influenza A virus poses ongoing global health and economic challenges due to its antigenic variability and pandemic potential. Current seasonal vaccines targeting the variable hemagglutinin (HA) provide limited and strain-specific protection. The conserved Matrix 2 Ectodomain (M2e) offers a promising universal vaccine target, eliciting protection by targeting infected cells rather than neutralizing virions. However, the mechanism underlying protection mediated by this simple antigen is complex, and no M2e-based vaccine has been licensed yet.
AREA COVERED
Precise M2e-vaccine optimization is needed. This review provides in-depth description of M2e established knowledge, as well as comparative studies using M2e-based vaccines. From this, the 'ideal archetype' of a universal vaccine including M2e will be defined. Finally, a review of the current preclinical nanoparticle based M2e vaccine will be provided, described, and analyzed.
EXPERT OPINION
Optimizing antigen presentation, evaluating Fc-mediated effector functions with standardized assays, and integrating M2e into multivalent nanoparticle platforms targeting complementary conserved antigens are likely to be key steps toward achieving broad, durable, and clinically translatable protection.
Louis Bourlon, J. Morlieras, P. Marche et al.· Expert Review of Vaccines· 0 citations
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