Abstract
Ebolavirus vaccines based on several adenoviral vectors have been investigated in preclinical studies and clinical trials. The use of adenovirus serotype 2 as a vector for ebolavirus vaccine has not been reported. Herein, we generated rAd2-ZGP, a recombinant replication-incompetent adenovirus serotype 2 expressing codon-optimized Zaire ebolavirus glycoprotein, and evaluated its immunogenicity in mice and rhesus macaques. rAd2-ZGP induced significant antibody and cell-mediated immune responses at 2 weeks after a single immunization. The glycoprotein (GP)-specific immune responses could be further enhanced with a booster immunization. Compared to protein antigens, Zaire ebolavirus GP and Zaire ebolavirus-like particles, rAd2-ZGP could induce stronger cross-reactive antibody and cell-mediated immune responses to heterologous Sudan ebolavirus in mice and rhesus macaques. In rAd2-ZGP-immunized macaques, GP-specific CD8+ T cells could secret IFN-γ and IL-2, indicating a Th1-biased response. In adenovirus serotype 5 seropositive macaques, rAd2-ZGP could induce robust antibody and cell-mediated immune responses, suggesting that the efficacy of rAd2-ZGP is not affected by pre-existing immunity to adenovirus serotype 5. These results demonstrated that rAd2-ZGP can be considered an alternative ebolavirus vaccine for use in adenovirus serotype 5 seropositive subjects or as a sequential booster vaccine after the subjects have been immunized with a recombinant adenovirus serotype 5-based vaccine.
Highlights
Ebolavirus (EBOV) belongs to a genus of the Filoviridae family and consists of five species, including Zaire, Sudan, Bundibugyo, Reston, and Taï Forest EBOVs1
enzyme-linked immunospot (ELISpot) responses to Zaire EBOV (ZEBOV) GP peptides, ZEBOV GP, and Sudan EBOV (SEBOV) GP in macaques immunized with recombinant human adenovirus serotype 2 (rAd2) vector carrying an unrelated Zika virus antigen, rAd2-zika, and we found no significant GP-specific cell-mediated immune (CMI) response in macaques immunized with rAd2-zika (Supplementary Figure S6)
We investigated in two animal species the antibody and CMI responses induced by rAd2-ZGP and, in parallel, by two protein-based EBOV vaccines, ZGP and ZVLPs
Summary
Ebolavirus (EBOV) belongs to a genus of the Filoviridae family and consists of five species, including Zaire, Sudan, Bundibugyo, Reston, and Taï Forest EBOVs1. Among these species, Zaire EBOV (ZEBOV) and Sudan EBOV (SEBOV) have the highest pathogenicity in humans[1]. The economic and health burdens posed by EBOV highlighted the need to develop safe and effective prophylactic vaccines. Recombinant adenoviruses (rAd) have been extensively explored as vaccine vectors for many pathogens, including HIV, mycobacterium tuberculosis, malaria, influenza virus, and EBOV4–7. RAd vectors expressing EBOV glycoprotein (GP), the major surface protein mediating the attachment and entry of EBOV8, effectively protected mice and non-human primates (NHPs) against lethal Recombinant adenoviruses (rAd) have been extensively explored as vaccine vectors for many pathogens, including HIV, mycobacterium tuberculosis, malaria, influenza virus, and EBOV4–7. rAd vectors expressing EBOV glycoprotein (GP), the major surface protein mediating the attachment and entry of EBOV8, effectively protected mice and non-human primates (NHPs) against lethal
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