RESUMO
The search for vaccines that protect from severe morbidity and mortality because of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Here we describe an amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol-poly(ethylene glycol) macromolecular amphiphile. It is water-soluble and exhibits massive translocation to lymph nodes upon local administration through binding to albumin, affording localized innate immune activation and reduction in systemic inflammation. The adjuvanticity of IMDQ-PEG-CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS-CoV-2 spike protein vaccine, showing robust IgG2a and IgG1 antibody titers in mice that could neutralize viral infection in vitro and in vivo in a mouse model.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Imidazóis/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Quinolinas/uso terapêutico , Animais , Vacinas contra COVID-19/imunologia , Colesterol/análogos & derivados , Colesterol/imunologia , Colesterol/uso terapêutico , Feminino , Humanos , Imidazóis/imunologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Glicoproteínas de Membrana/agonistas , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Polietilenoglicóis/uso terapêutico , Quinolinas/imunologia , Proteínas Recombinantes/imunologia , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/imunologia , Tensoativos/uso terapêutico , Receptor 7 Toll-Like/agonistas , Receptor 8 Toll-Like/agonistasRESUMO
Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine candidate based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here, we show that the NDV vector expressing an optimized spike antigen (NDV-HXP-S) is a versatile vaccine inducing protective antibody responses. NDV-HXP-S can be administered intramuscularly as inactivated vaccine or intranasally as live vaccine. We show that NDV-HXP-S GMP-produced in Vietnam, Thailand and Brazil is effective in the hamster model. Furthermore, we show that intramuscular vaccination with NDV-HXP-S reduces replication of tested variants of concerns in mice. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters.