An adenovirus serotype 2-vectored ebolavirus vaccine generates robust antibody and cell-mediated immune responses in mice and rhesus macaques

• DOI: 10.1038/s41426-018-0102-5
• Publication Date: 2018-05-31T13:15:36Z
• Authors: Yupeng Feng; Chufang Li; Peiyu Hu; Qian Wang; Xuehua Zheng; Yongkun Zhao; Yi Shi; Songtao Yang; Changhua Yi; Ying Feng; Chunxiu Wu; Linbing Qu; Wei Xu; Yao Li; Caijun Sun; Fu Geroge Gao; Xianzhu Xia; Liqiang Feng; Ling Chen
• Keywords: Male; Immunity, Cellular; Mice, Inbred BALB C; 0303 health sciences; T-Lymphocytes; Vaccination; Viral Vaccines; Hemorrhagic Fever, Ebola; Antibodies, Viral; Ebolavirus; Macaca mulatta; Article; Adenoviridae; 3. Good health; Disease Models, Animal; Interferon-gamma; Mice; Viral Proteins; 03 medical and health sciences; Animals; Humans; Interleukin-2; Female; Glycoproteins

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.