Molecular Therapy: Methods & Clinical Development (Sep 2023)
Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine
- Ekramy E. Sayedahmed,
- Marcelo Valdemir Araújo,
- Taiana Tainá Silva-Pereira,
- Shubhada K. Chothe,
- Ahmed Elkashif,
- Marwa Alhashimi,
- Wen-Chien Wang,
- Andrea P. Santos,
- Meera Surendran Nair,
- Abhinay Gontu,
- Ruth Nissly,
- Antônio Francisco de Souza Filho,
- Mariana Silva Tavares,
- Marina Caçador Ayupe,
- Caio Loureiro Salgado,
- Érika Donizetti de Oliveira Candido,
- Danielle Bruna Leal Oliveira,
- Edison Luiz Durigon,
- Marcos Bryan Heinemann,
- Denise Morais da Fonseca,
- Chinnaswamy Jagannath,
- Ana Marcia Sá Guimarães,
- Suresh V. Kuchipudi,
- Suresh K. Mittal
Affiliations
- Ekramy E. Sayedahmed
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN, USA
- Marcelo Valdemir Araújo
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Butantan Institute, São Paulo, Brazil
- Taiana Tainá Silva-Pereira
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Shubhada K. Chothe
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA
- Ahmed Elkashif
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN, USA
- Marwa Alhashimi
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN, USA
- Wen-Chien Wang
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN, USA
- Andrea P. Santos
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN, USA
- Meera Surendran Nair
- Department of Veterinary and Biomedical Sciences, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA; Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA
- Abhinay Gontu
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA
- Ruth Nissly
- Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA
- Antônio Francisco de Souza Filho
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Mariana Silva Tavares
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Marina Caçador Ayupe
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Caio Loureiro Salgado
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Érika Donizetti de Oliveira Candido
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Danielle Bruna Leal Oliveira
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Edison Luiz Durigon
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Marcos Bryan Heinemann
- Department of Preventive Veterinary Medicine and Animal Health, College of Veterinary Medicine, University of São Paulo, São Paulo, Brazil
- Denise Morais da Fonseca
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Chinnaswamy Jagannath
- Department of Pathology and Genomic Medicine, Center for Infectious Diseases and Translational Medicine, Houston Methodist Research Institute, Houston, TX, USA; Weill Cornell Medical College, New York, NY, USA
- Ana Marcia Sá Guimarães
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Corresponding author: Ana Marcia Sá Guimarães, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
- Suresh V. Kuchipudi
- Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA; Corresponding author: Suresh V. Kuchipudi, Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA.
- Suresh K. Mittal
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN, USA; Corresponding author: Suresh K. Mittal, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 625 Harrison St, West Lafayette, IN 47907-2027, USA.
- Journal volume & issue
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Vol. 30
pp. 194 – 207
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 adenovirus (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 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 with HAd-Spike vaccinated groups. These results indicated 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 challenge. 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.
