Despite substantial improvements, influenza vaccine production-and availability-remain suboptimal. Influenza vaccines based on mRNA may offer a solution as sequence-matched, clinical-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. Here we show that mRNA vaccines induce balanced, long-lived and protective immunity to influenza A virus infections in even very young and very old mice and that the vaccine remains protective upon thermal stress. This vaccine format elicits B and T cell-dependent protection and targets multiple antigens, including the highly conserved viral nucleoprotein, indicating its usefulness as a cross-protective vaccine. In ferrets and pigs, mRNA vaccines induce immunological correlates of protection and protective effects similar to those of a licensed influenza vaccine in pigs. Thus, mRNA vaccines could address substantial medical need in the area of influenza prophylaxis and the broader realm of anti-infective vaccinology.
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http://dx.doi.org/10.1038/nbt.2436 | DOI Listing |
Biomaterials
December 2024
Center for Inflammation, Immunity & Infection, Institute for Biomedical Science, Georgia State University, Atlanta, GA, USA. Electronic address:
The rapid approval of SARS-CoV-2 mRNA lipid nanoparticle (LNP) vaccines indicates the versatility of mRNA LNPs in an urgent vaccine need. However, the mRNA vaccines do not induce mucosal cellular responses or broad protection against recent variants. To improve cross-protection of mRNA vaccines, here we engineered a pioneered mRNA LNP encapsulating with mRNA constructs encoding cytokine adjuvant and influenza A hemagglutinin (HA) antigen for intradermal vaccination.
View Article and Find Full Text PDFAdv Healthc Mater
December 2024
Department of Biomedical Sciences, Biomedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School, 322 Seoyang-ro, Hwasun, 58128, Republic of Korea.
Advancements in mRNA delivery nanoparticles have significantly improved the potential for treating challenging diseases. Due to the inherent immunogenicity and rapid degradation of mRNA, specialized nanoparticles are required for efficient intracellular uptake, endosomal escape, and protection from lysosomal degradation. Although current methods enable transgene expression but achieving a balance between efficiency and toxicity remains challenging.
View Article and Find Full Text PDFNPJ Vaccines
December 2024
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
We previously reported that mice immunized twice with a lipid nanoparticle vaccine comprising four monkeypox viral mRNAs raised neutralizing antibodies and antigen-specific T cells and were protected against a lethal intranasal challenge with vaccinia virus (VACV). Here we demonstrated that the mRNA vaccine also protects mice against intranasal and intraperitoneal infections with monkeypox virus and bioluminescence imaging showed that vaccination greatly reduces or prevents VACV replication and spread from intranasal, rectal, and dermal inoculation sites. A single vaccination provided considerable protection that was enhanced by boosting for at least 4 months.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.
View Article and Find Full Text PDFJ Korean Med Sci
December 2024
Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Background: This study aimed to investigate the epidemiological characteristics and outcomes of myocarditis/pericarditis after BNT162b2 vaccination in Korean adolescents.
Methods: This was a retrospective cohort analysis of adolescents aged 12-19 years old diagnosed with myocarditis/pericarditis within 42 days of BNT162b2 mRNA vaccination. All reported cases were investigated by city or government epidemiologists and the diagnostic certainty and causality was determined by the Korea Disease Control and Prevention Agency's Adverse Event Following Immunization Expert Advisory Committee according to the modified version of Brighton Collaboration Myocarditis/Pericarditis Working group's case definitions.
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