Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenoviral vectored SARS-CoV-2 vaccine expressing the spike protein

• Published in: Molecular therapy. Methods & clinical development 2023-06
• Main Authors: Sayedahmed, Ekramy E., Araújo, Marcelo Valdemir, Silva-Pereira, Taiana Tainá, Chothe, Shubhada K., Elkashif, Ahmed, Alhashimi, Marwa, Wang, Wen-Chien, Santos, Andrea P., Nair, Meera Surendran, Gontu, Abhinay, Nissly, Ruth, Francisco de Souza Filho, Antônio, Tavares, Mariana Silva, Ayupe, Marina Caçador, Salgado, Caio Loureiro, Donizetti de Oliveira Candido, Érika, Leal Oliveira, Danielle Bruna, Durigon, Edison Luiz, Heinemann, Marcos Bryan, Morais da Fonseca, Denise, Jagannath, Chinnaswamy, Sá Guimarães, Ana Marcia, Kuchipudi, Suresh V., Mittal, Suresh K.
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2329-0501
• DOI: 10.1016/j.omtm.2023.06.009

Due to a 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 adenoviral (Ad) vector-based vaccines (HAd-Spike/C5 and HAd-Spike) that express the whole spike (S) protein of SARS-CoV-2 with or without an autophagy-inducing peptide C5 (AIP-C5), respectively. Mice or Golden Syrian hamsters immunized intranasally (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 to HAd-Spike vaccinated groups. These results alluded that the 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 turbinate were collected at 3-, 5-, 7-, and 14 days post-challenge. Significant reductions in morbidity, virus titers, and lung histopathological scores were observed in immunized groups compared to the mock- or the empty vector-inoculated groups. Overall, slightly better protection was seen in the HAd-Spike/C5 group compared to the HAd-Spike group. Mittal and his colleagues demonstrated that the adenoviral vector expressing the spike protein of SARS-CoV-2 with an autophagy-inducing peptide C5 (AIP-C5) enhances cell-mediated immune responses - critical for targeting SARS-CoV-2 variants. Improved immune responses and protection were observed in immunized hamsters, suggesting the importance of AIP-C5 in the vaccine design.