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1.
Emerg Microbes Infect ; 11(1): 914-925, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35254215

ABSTRACT

Infection caused by respiratory viruses can lead to a severe respiratory disease and even death. Vaccination is the most effective way to prevent the disease, but it cannot be quickly applied when facing an emerging infectious disease. Here, we demonstrated that immunization with an aluminium-zinc hybrid particulate adjuvant (FH-001) alone, bearing great resemblance in morphology with commonly used aluminium-based adjuvants in vaccines, could quickly induce mice to generate a broadly protective immune response to resist the lethal challenge of influenza B viruses. Furthermore, a multi-omics-based analysis revealed that the alveolar macrophage and type I interferon pathway, rather than adaptive immunity and type II interferon pathway, were essential for the observed prophylactic effect of FH-001. More importantly, a similar protective effect was observed against influenza A virus strain A/Shanghai/02/2013(H7N9), A/California/04/2009(H1N1) and respiratory syncytial virus. Therefore, we introduced here a new and promising strategy that can be quickly applied during the outbreak of emerging respiratory viruses.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Orthomyxoviridae Infections , Adjuvants, Immunologic , Aluminum , Animals , Antibodies, Viral , China , Immunity, Innate , Mice , Mice, Inbred BALB C
2.
Sci Transl Med ; 13(606)2021 08 11.
Article in English | MEDLINE | ID: mdl-34285130

ABSTRACT

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.


Subject(s)
COVID-19 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Cricetinae , Humans , Mice , Protein Subunits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
3.
Expert Rev Vaccines ; 16(9): 895-906, 2017 09.
Article in English | MEDLINE | ID: mdl-28712326

ABSTRACT

INTRODUCTION: Adjuvants are essential components in vaccine formulations to induce robust immunity against pathogens. The most widely used adjuvants in human vaccines are aluminum salts, that can effectively elicit a T helper type-2 (Th2)-biased humoral immune response for producing a high antibody titer but with a limited cellular immune response. Biocompatible calcium phosphate nanoparticles (CaP-NPs) with tunable characteristics have potentials to function as adjuvants for inducing more balanced T helper type-1 (Th1) and Th2 immune responses. Areas covered: Here we review the preparation procedures and characteristics of CaP-NPs. The process can be well-controlled and readily scaled up. Antigen loading can take place as encapsulation during the particle formation or as passive adsorption post particle formation. Different modalities of immunogens were tested with CaP-NPs as adjuvants. The possible mechanisms of the CaP-NP-based adjuvants are discussed. Expert commentary: With good adjuvant effects and safety profiles, CaP-NPs have the potentials to be a new generation vaccine adjuvant. A more in-depth understanding of the mechanisms of their adjuvanticity could facilitate the process optimization for making adjuvants with preferred characteristics. Interdisciplinary collaborations are essential for testing the biocompatible CaP-NPs in human vaccines for clinical development and eventually for use in marketed vaccines.


Subject(s)
Adjuvants, Immunologic/pharmacology , Antigens/immunology , Calcium Phosphates/pharmacology , Nanoparticles , Th1 Cells/drug effects , Th2 Cells/drug effects , Adjuvants, Immunologic/administration & dosage , Animals , Antigens/administration & dosage , Calcium Phosphates/administration & dosage , Humans , Th1 Cells/immunology , Th2 Cells/immunology
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