Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine

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Sayedahmed, Ekramy E. ; Araujo, Marcelo Valdemir ; Silva-Pereira, Taiana Taina ; Chothe, Shubhada K. ; Elkashif, Ahmed ; Alhashimi, Marwa ; Wang, Wen-Chien ; Santos, Andrea P. ; Nair, Meera Surendran ; Gontu, Abhinay ; Nissly, Ruth ; de Souza Filho, Antonio Francisco ; Tavares, Mariana Silva ; Ayupe, Marina Cacador ; Salgado, Caio Loureiro ; Candido, erika Donizetti de Oliveira ; Oliveira, Danielle Bruna Leal ; Durigon, Edison Luiz ; Heinemann, Marcos Bryan ; da Fonseca, Denise Morais ; Jagannath, Chinnaswamy ; Guimaraes, Ana Marcia Sa ; Kuchipudi, Suresh, V ; Mittal, Suresh K.

• Document type: Journal article
• Source: MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT; v. 30, p. 14-pg., 2023-09-14.

Abstract

Because of continual generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to design the next generation of vaccines to combat the threat posed by SARS-CoV-2 variants. We developed human adeno-virus (HAd) vector-based vaccines (HAd-Spike/C5 and HAd-Spike) that express the whole Spike (S) protein of SARS-CoV-2 with or without autophagy-inducing peptide C5 (AIP-C5), respectively. Mice or golden Syrian hamsters immunized intra-nasally (i.n.) with HAd-Spike/C5 induced similar levels of S-specific humoral immune responses and significantly higher levels of S-specific cell-mediated immune (CMI) responses compared with HAd-Spike vaccinated groups. These results indi-cated that inclusion of AIP-C5 induced enhanced S-specific CMI responses and similar levels of virus-neutralizing titers against SARS-CoV-2 variants. To investigate the protection efficacy, golden Syrian hamsters immunized i.n. either with HAd-Spike/ C5 or HAd-Spike were challenged with SARS-CoV-2. The lungs and nasal turbinates were collected 3, 5, 7, and 14 days post chal-lenge. Significant reductions in morbidity, virus titers, and lung histopathological scores were observed in immunized groups compared with the mock-or empty vector-inoculated groups. Overall, slightly better protection was seen in the HAd-Spike/ C5 group compared with the HAd-Spike group. (AU)

• FAPESP's process: 19/13916-0 - Study of the tissue-specific response during exposure of the intestinal mucosa to bacterial toxins
• Grantee: Caio Loureiro Salgado
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/12691-4 - Gut-lung axis: contribution of diet and intestinal microbiota to the regulation of lung mucosa-associated immune system
• Grantee: Marina Caçador Ayupe
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/09149-0 - Evaluation of Syrian hamsters (Mesocricetus auratus) as an experimental model of SARS-CoV-2 infection and disease
• Grantee: Antonio Francisco de Souza Filho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/07251-2 - Evaluation of Syrian hamsters (Mesocricetus auratus) as model of infection and disease by SARS-CoV-2
• Grantee: Ana Marcia de Sá Guimarães
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease
• Grantee: Denise Morais da Fonseca
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 21/02736-0 - Good practices and operation of biosafety level 3+ laboratories
• Grantee: Mariana Silva Tavares
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training