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Development of SARS-CoV-2 auto-assembly protein-based nanovaccines

Abstract

The sudden appearance of a new viral pneumonia in late 2019 was the first of a series of events that led the world to a pandemic that in only 3 months has infected over one million people and reached over 200 countries and territories. The virus, named SARS-CoV-2, from the Coronaviridae family just like SARS and MERS, triggers a severe acute respiratory disease that leads to death in approximately 2% of the cases. The disease COVID-19 has already caused unmeasurable global impacts and is likely to be contained only through the development of vaccines, since new waves of infection may occur once suppression measurements are suspended. The World Health Organization states that vaccines are now a major priority in this battle. In such a fragile scenario that involves the need to vaccinate as soon as possible people belonging to the risk groups, safer strategies such as subunit vaccines should be a priority. The low immunogenicity frequently associated with this strategy can be counteracted by the use of nanoparticles that allow a multivalent antigen presentation, leading to a more robust immunological response. In the present project, we propose the use of SAPN (Self Assembling Protein Nanoparticles) strategy to develop the nanovaccines, which consists in modifying the protein antigen with the fusion of short peptide sequences that promote self-assembly in nanoparticles (NP) of around 100 nm in adequate physicochemical conditions. Such strategy mimics the antigen display of a viral particle and is currently being used by our group in a ZIKV model, inducing a strong antigen-specific humoral response. Different structural antigens of SARS-CoV-2 will be selected to be transformed into nanovaccines through the proposed strategy, which will be used to induce protective immunological responses (antibodies) capable to inhibit virus infectivity at in vitro conditions and, subsequently, protective immunity in murine model. As a plus, these nanovaccines also present improved stability and higher internalization capacity, since they have in their structure peptides that act as Cell Penetrating Peptides, thus mimicking not only the size but also the behavior of viral particles, what can favor cellular immunity. We seek to develop an innovative vaccine strategy that can strongly contribute to this pandemic and be shortly considered a promising tool to be used to limit COVID-19 spread. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (7)
(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)
DAHER, ISABELA PAZOTTI; ALMEIDA, BIANCA DA SILVA; DE SOUZA-SILVA, GUILHERME ANTONIO; MARQUES, RODOLFO FERREIRA; SOARES, GUSTAVO HENRIQUE CORREA; ANDREATA-SANTOS, ROBERT; MORETTI, ANA; SILVA, MARIANGELA DE OLIVEIRA; SCHUCH, VIVIANE; SASAHARA, GREYCE LURI; et al. Neutralizing antibody responses after a two-dose regimen with BNT162b2 CoronaVac or ChAdOx1-S in Brazil: Differential neutralization of SARS-CoV-2 omicron variants. Clinical Immunology, v. 276, p. 12-pg., . (21/14197-7, 14/50890-5, 21/13004-0, 18/07142-9, 20/05204-7)
SOUZA, MILENA SILVA; FARIAS, JESSICA PIRES; ANDREATA-SANTOS, ROBERT; SILVA, MARIANNE PEREIRA; BRITO, RUTH DALETY DA SILVA; DUARTE BARBOSA DA SILVA, MARCIA; PETER, CRISTINA MENDES; CIRILO, MARCUS VINICIUS DE FRANCA; LUIZ, WILSON BARROS; BIRBRAIR, ALEXANDER; et al. Neutralizing antibody response after immunization with a COVID-19 bivalent vaccine: Insights to the future. Journal of Medical Virology, v. 96, n. 2, p. 9-pg., . (20/06409-1, 23/01925-0, 20/08943-5, 22/11981-1, 21/05661-1, 20/05204-7)
PIRES FARIAS, JESSICA; SOUZA, MILENA SILVA; COSTA FOGACA, MAYANNA MOREIRA; DA SILVA BRITO, RUTH DALETY; DA ROCHA SANTOS, AMANDA; DE MELO, CRISTIANE MOUTINHO LAGOS; DE SOUSA, GEORON FERREIRA; BRACONI, CARLA TORRES; LOPES BARBOZA, MARIO GABRIEL; DE SOUZA LINO, VANESCA; et al. Antigenic drift in SARS-CoV-2: diminished vaccine protection in pediatric populations against Omicron and its JN.1 subvariant. EXPERT REVIEW OF VACCINES, v. 24, n. 1, p. 9-pg., . (22/11981-1, 23/01925-0, 23/07746-0, 20/06409-1, 20/05204-7)
RODRIGUES-JESUS, MONICA JOSIANE; FAVARO, MARIANNA TEIXEIRA DE PINHO; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; DE CASTRO-AMARANTE, MARIA FERNANDA; ALMEIDA, BIANCA DA SILVA; SILVA, MARIANGELA DE OLIVEIRA; ANDREATA-SANTOS, ROBERT; BARBOSA, CECILIA GOMES; BRITO, SAMANTHA CARVALHO MAIA; FREITAS-JUNIOR, LUCIO H.; et al. Nano-multilamellar lipid vesicles promote the induction of SARS-CoV-2 immune responses by a protein-based vaccine formulation. Nanomedicine-Nanotechnology Biology and Medicine, v. 45, p. 11-pg., . (20/10700-3, 20/08943-5, 16/23560-0, 20/05204-7, 21/05661-1)
FARIAS, JESSICA PIRES; ANDREATA-SANTOS, ROBERT; BRITO, RUTH DALETY DA SILVA; SOUZA, MILENA SILVA; FOGACA, MAYANNA MOREIRA COSTA; PINHEIRO, JOSILENE RAMOS; DA CRUZ, EDGAR FERREIRA; LIANG, WILLIAN; SIMOES, RAFAEL DA CONCEICAO; LUIZ, WILSON BARROS; et al. The fourth COVID-19 vaccine dose increased the neutralizing antibody response against the SARS-CoV-2 Omicron (B.1.1.529) variant in a diverse Brazilian population. MICROBIOLOGY SPECTRUM, v. N/A, p. 16-pg., . (20/05204-7, 21/05661-1, 20/08943-5, 22/11981-1)
REGO, LAYANE SOUZA; FAVARO, MARIANNA TEIXEIRA PINHO; RODRIGUES-JESUS, MONICA JOSIANE; ANDREATA-SANTOS, ROBERT; JANINI, LUIZ MARIO RAMOS; SECKLER, MARCELO MARTINS; FERREIRA, LUIS CARLOS DE SOUZA; AZZONI, ADRIANO RODRIGUES. Amino Compound-Synthesized Gold Nanoparticles for SARS-CoV-2 Antigen Delivery. PHARMACEUTICS, v. 17, n. 9, p. 15-pg., . (23/01153-7, 20/05204-7, 21/05661-1, 20/08943-5, 23/16234-2, 20/10700-3)
APS, LUANA RAPOSO DE MELO MORAES; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; DE FREITAS, CARLA LONGO; PORCHIA, BRUNA FELICIO MILAZZOTTO MALDONADO; SILVA, MARIANGELA DE OLIVEIRA; PEREIRA, LENNON RAMOS; SALES, NATIELY SILVA; PELEGRIN, GUILHERME FORMOSO; SEGABINAZI, ETHIANE; RODRIGUES, KARINE BITENCOURT; et al. T-Cell Epitope-Based SARS-CoV-2 DNA Vaccine Encoding an Antigen Fused with Type 1 Herpes Simplex Virus Glycoprotein D (gD). Viruses-Basel, v. 17, n. 9, p. 19-pg., . (23/01925-0, 20/05204-7, 23/01153-7, 21/05698-2, 24/03895-3, 20/13640-1)