An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 21, 2024

Abstract Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) influenza viruses continue to pose a global health burden. Thus, we developed chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 virus. When used as standalone intranasal immunization AdC68-HATRBD induced comprehensive potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, memory T cells, which protected mice from BA.5.2 pandemic H1N1 infections. heterologous booster, markedly improved protective response licensed or vaccine. Therefore, whether administered intranasally booster this vaccine is valuable strategy enhance overall efficacy by inducing robust systemic responses, thereby conferring lines immunological defenses for these two viruses.

Language: Английский

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A-910823, a squalene-based emulsion adjuvant, enhances robust and broad immune responses of quadrivalent influenza vaccine in ferrets

Vaccine, Journal Year: 2025, Volume and Issue: 49, P. 126780 - 126780

Published: Jan. 30, 2025

Language: Английский

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Epitope-focused vaccine immunogens design using tailored horseshoe-shaped scaffold

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 18, 2025

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants highlights the need to update coronavirus 2019 disease (COVID-19) vaccine components. Epitope-based designs targeting conserved and immunorecessive regions SARS-CoV-2 are critically needed. Here, we report an engineered epitope-focused immunogen design based on a novel horseshoe-shaped natural protein scaffold, named ribonuclease inhibitor 1 (RNH1), that can multiply display neutralizing epitopes from S2 stem helix. designed RNH1-S1139 demonstrates high binding affinity S2-specific antibodies elicits robust epitope-targeted antibody responses either through homologous or heterologous vaccination regimens. immune serum has been proven have similar ability against SARS-CoV, its variants, providing broad-spectrum protection as membrane fusion inhibitor. Further studies showed RNH1 potential serve versatile scaffold displays other helical various antigens, including syncytial virus (RSV) F glycoprotein. Our proposed engineering strategy via tailored horseshoe-shape nano-scaffold supports continued development vaccines part next-generation design.

Language: Английский

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Longitudinal analysis of immune responses to SARS-CoV-2 recombinant vaccine S-268019-b in phase 1/2 prime-boost study

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 5, 2025

The durability of vaccine-induced immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for preventing infection, especially disease. This follow-up report from a phase 1/2 study S-268019-b (a recombinant spike protein vaccine) after homologous booster vaccination confirms its long-term safety, tolerability, and immunogenicity. Booster with resulted in an enhancement serum neutralizing antibody (NAb) titers broad range viral neutralization. Single-cell profiling revealed persistent mature antigen-specific B cells T follicular helper cells, increased B-cell receptor diversity. expansion B- T-cell repertoires presence cross-reactive NAbs targeting conserved epitopes within the receptor-binding domain following accounted broad-spectrum activity. These findings highlight potential provide robust protection against SARS-CoV-2 variants, addressing critical challenge ongoing fight disease 2019 (COVID-19).

Language: Английский

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Broad Mucosal and Systemic Immunity in Mice Induced by Intranasal Booster With a Novel Recombinant Adenoviral Based Vaccine Protects Against Divergent Influenza A Virus

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(4)

Published: March 27, 2025

ABSTRACT The development of broad‐spectrum universal influenza vaccines and optimization vaccination strategies to address the threats posed by pandemics emerging viruses are critical for public health. In this study, an adenovirus type 5 vector‐based vaccine carrying hemagglutinin (HA) stem H1, HA H3, neuraminidase (NA) N1 from virus was constructed. Immune responses were evaluated in mice using various strategies: prime‐only (intramuscular [IM] or intranasal [IN]) prime‐boost (IM + IN). Compared with strategy, strategy significantly enhanced systemic immune response, inducing higher levels antigen‐specific IgG, mucosal IgA, T cell immunity spleen lungs. Furthermore, IN boosting provided complete protection challenged H1N1‐PR8, rgH3N2‐X31, rgH5N1‐Vietnam viruses, reducing viral loads lungs alleviating lung tissue pathologies. conclusion, study elucidates potential avenues application customized strategies.

Language: Английский

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RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 30, 2025

Abstract The SARS-CoV-2 pandemic revealed the rapid evolution of circulating strains. This led to new variants carrying mostly mutations within receptor binding domain, which is immunodominant upon immunization and infection. In order steer immune response away from RBD epitopes more conserved domains, we generated S glycoprotein trimers without stabilized them by formaldehyde cross-linking. cryoEM structure demonstrated that SΔRBD folds into native prefusion conformation, one specific cross-link between S2 protomers. was coated onto lipid vesicles, produce synthetic virus-like particles, SΔRBD-LV, were utilized in a heterologous prime-boost strategy. Immunization cynomolgus macaques either three times with mRNA Comirnaty vaccine or two followed SΔRBD-LV showed boost induced similar antibody titers neutralization different variants, including omicron. Upon challenge omicron XBB.3, both only Comirnaty/SΔRBD-LV vaccination schemes conferred overall protection infection for schemes. However, indicated better against lung than strategy alone. Together our findings indicate highly immunogenic provides improved compared third indicative superior antibody-based protection.

Language: Английский

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A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 20, 2023

Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently in clinical development. Published evidence has demonstrated can induction neutralizing antibodies SARS-CoV-2 humans and animal models. However, characteristics mechanisms immune responses induced by not yet known. To characterize A-910823, we compared adaptive response profile enhanced with other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, empty lipid nanoparticle [eLNP]) murine model. Compared humoral to an equal greater extent following potent T follicular helper (Tfh) germinal center B (GCB) cell induction, without inducing strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing produced similar results even when given as booster dose primary administration nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation modified identify which components play role driving effect detailed evaluation immunological each showed immunity Tfh GCB were dependent on α-tocopherol. Finally, revealed recruitment cells draining lymph nodes serum cytokines chemokines also α-tocopherol component. This study demonstrates capable robust responses, dose. The findings emphasize drives Tfh-inducing function A-910823. Overall, our data provide key information may inform future production improved adjuvants.

Language: Английский

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The evolution of SARS-CoV-2 and the COVID-19 pandemic

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e15990 - e15990

Published: Sept. 7, 2023

Scientists have made great efforts to understand the evolution of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) provide crucial information public health experts on strategies control this viral pathogen. The pandemic coronavirus disease that began in 2019, COVID-19, lasted nearly three years, and all countries set different epidemic prevention policies for virus. continuous alters its pathogenicity infectivity human hosts, thus policy treatments been continually adjusted. Based our previous study dynamics binding ability prediction between COVID-19 spike protein ACE2, present mined over 10 million sequences epidemiological data during 2020-2022 evolutionary path SARS-CoV-2. We analyzed predicted mutation rates whole genome main proteins from populations adaptive relationship humans COVID-19. Our identified a correlation each various populations. Overall, analysis provides scientific basis developing data-driven confront pathogens.

Language: Английский

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Impact of SARS-CoV-2 vaccination on FcγRIIIA/CD16 dynamics in Natural Killer cells: relevance for antibody-dependent functions

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 16, 2023

Natural Killer (NK) cells contribute to the protective effects of vaccine-induced antibodies thanks low affinity receptor for IgG, FcγRIIIA/CD16, whose aggregation leads killing infected and IFNγ release, through which they potentiate adaptive immune responses. Forty-seven healthy young individuals undergoing either homologous (ChAdOx1-S/ChAdOx1-S) or heterologous (ChAdOx1-S/BNT162B2) SARS-CoV-2 vaccination settings were recruited. Peripheral blood samples collected immediately prior 8 weeks after booster dose. The phenotypic functional profile NK was evaluated by flow cytometry at both time points. Serum tested evaluate circulating anti-Spike IgG levels cytomegalovirus serostatus. CD16 F158V polymorphism assessed sequencing analysis. downregulation selective impairment antibody-dependent cytotoxicity production in CD56dim population, persisting boosting, observed heterologous, but not scheme. While magnitude CD16-dependent functions global pool correlated with before vaccination, responsivity NKG2C+ subset, that displays amplified size functionality HCMV+ individuals, resulted intrinsically insensitive levels. Individual responsiveness also affected CD16F158V polymorphism; F/F characterized reduced independently did show post-vaccinal respect intermediate high ones, despite a comparable downregulation. Further, ligation conditions means afucosylated mAb overcame genotype-dependent defects. Finally, preservation expression directly titer, hinting individual receptor-dependent may amplification vaccinal response. This study demonstrates durable downmodulation Ab-dependent highlights impact genetic environmental host-related factors modulating cell susceptibility Fc-dependent impairment.

Language: Английский

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Microfluidic particle counter visualizing mucosal antibodies against SARS-CoV-2 in the upper respiratory tract for rapid evaluation of immune protection

Lab on a Chip, Journal Year: 2024, Volume and Issue: 24(10), P. 2658 - 2668

Published: Jan. 1, 2024

A microfluidic particle counter for visualizing mucosal antibody levels against SARS-CoV-2 in the upper respiratory tract rapid evaluation of immune protection.

Language: Английский

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