TY - JOUR
T1 - A multi-antigen-based SARS-CoV-2 vaccine provides higher immune responses and protection against SARS-CoV-2 variants
AU - Alhashimi, Marwa
AU - Sayedahmed, Ekramy E.
AU - Elkashif, Ahmed
AU - Chothe, Shubhada K.
AU - Wang, Wen Chien
AU - Murala, Muralimanohara S.T.
AU - Gairola, Vivek
AU - Wakamatsu, Nobuko
AU - Gontu, Abhinay
AU - Ramasamy, Santhamani
AU - LaBella, Lindsey
AU - Jakka, Padmaja
AU - Surendran Nair, Meera
AU - Nissly, Ruth H.
AU - Kuchipudi, Suresh Varma
AU - Mittal, Suresh K.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - The emergence of divergent SARS-CoV-2 variants has significantly compromised the effectiveness of first-generation COVID-19 vaccines. We investigated a prime-boost approach using bovine adenoviral (Ad) [BAd] and human Ad (HAd) vectors expressing the spike (S), membrane (M), or nucleocapsid (N) with the autophagy-inducing peptide C5 (AIP-C5) for enhanced antigen-specific immunity. The combinational vaccine formulation expressing three antigens demonstrated markedly elevated antigen-specific cell-mediated immune (CMI) responses compared to groups immunized with vectors expressing individual antigens. Furthermore, vaccinated animals exhibited 100% survival, significant reductions in lung viral titers, and no apparent signs of morbidity following challenges with Delta or Omicron variants in K18-hACE2 transgenic mice. Surprisingly, immunization with vectors expressing M and N resulted in immune suppression. However, including S with M and N overcomes this antagonistic interaction and significantly enhances immune responses and protection efficacy. Using the BAd vaccine platform in a multi-antigen approach complemented with AIP-C5 is a promising strategy for developing next-generation SARS-CoV-2 vaccines.
AB - The emergence of divergent SARS-CoV-2 variants has significantly compromised the effectiveness of first-generation COVID-19 vaccines. We investigated a prime-boost approach using bovine adenoviral (Ad) [BAd] and human Ad (HAd) vectors expressing the spike (S), membrane (M), or nucleocapsid (N) with the autophagy-inducing peptide C5 (AIP-C5) for enhanced antigen-specific immunity. The combinational vaccine formulation expressing three antigens demonstrated markedly elevated antigen-specific cell-mediated immune (CMI) responses compared to groups immunized with vectors expressing individual antigens. Furthermore, vaccinated animals exhibited 100% survival, significant reductions in lung viral titers, and no apparent signs of morbidity following challenges with Delta or Omicron variants in K18-hACE2 transgenic mice. Surprisingly, immunization with vectors expressing M and N resulted in immune suppression. However, including S with M and N overcomes this antagonistic interaction and significantly enhances immune responses and protection efficacy. Using the BAd vaccine platform in a multi-antigen approach complemented with AIP-C5 is a promising strategy for developing next-generation SARS-CoV-2 vaccines.
UR - https://www.scopus.com/pages/publications/105011190041
UR - https://www.scopus.com/pages/publications/105011190041#tab=citedBy
U2 - 10.1038/s41541-025-01198-7
DO - 10.1038/s41541-025-01198-7
M3 - Article
C2 - 40683879
AN - SCOPUS:105011190041
SN - 2059-0105
VL - 10
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 159
ER -
