Heterologous prime-boost regimens with Ad5 and NDV vectors elicit stronger immune responses to Ebola virus than homologous regimens in mice

Authors: ZHAO, WEI - Chinese Center For Disease Control; ZHANG, PENG - Chinese Center For Disease Control; BAI, SHUANG - Chinese Center For Disease Control; LV, MIN - Chinese Center For Disease Control; WANG, JIAN - Chinese Center For Disease Control; CHEN, WEIXIN - Chinese Center For Disease Control; Yu, Qingzhong; WU, JIANG - Chinese Center For Disease Control

Submitted to: Archives of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2021
Publication Date: 9/30/2021
Citation: Zhao, W., Zhang, P., Bai, S., Lv, M., Wang, J., Chen, W., Yu, Q., Wu, J. 2021. Heterologous prime-boost regimens with Ad5 and NDV vectors elicit stronger immune responses to Ebola virus than homologous regimens in mice. Archives of Virology. https://doi.org/10.1007/s00705-021-05234-4.
DOI: https://doi.org/10.1007/s00705-021-05234-4

Interpretive Summary: Ebola virus disease (EVD) is a severe, often fatal illness affecting humans and other primates. The virus is transmitted to people from wild animals (such as fruit bats and non-human primates) and then spreads in the human population through direct contact with the blood, secretions, organs or other bodily fluids of infected people. There is no proven treatment and vaccine for EVD. An adenovirus type 5 (Ad5) vectored experimental EVD vaccine known as Ad5-MakGP could elicit robust humoral responses when immunized twice with a prime-boost regimen but induce little cellular immune responses. It is suspected that the preexisting immunity (PEI) to the Ad5 vector suppresses the cellular immune responses. To overcome the Ad5 preexisting immunity interference, we developed a Newcastle disease virus (NDV) vectored Ebola vaccine candidate (rLS/EB-GP) using reverse genetics technology. Vaccination of mice with Ad5-MakGP (prime) followed by rLS/EB-GP (boost) induced more potent Ebola virus GP-specific antibody and T-cell responses than Ad5 or NDV homologous prime-boost immunization regimens. The results suggest that the rLS/EB-GP is a promising EVD vaccine that can boost both humoral and cellular immune responses in the heterologous immunization regimen.

Technical Abstract: The 2014 Ebola outbreak in West Africa resulted in more than 11,000 deaths, highlighted the need for a vaccine. A Phase I clinical trial of adenovirus type 5 (Ad5) vector-based EBOV vaccine has shown that a homologous prime-boost regimen with Ad5 vaccine could elicit robust humoral responses, but little cellular immune responses. Here, we generated a recombinant Newcastle disease virus (NDV), based on the LaSota vaccine strain, expressing EBOV variant Makona GP protein (rLS/EB-GP) using reverse genetics technology. The humoral and cellular immune responses to this vaccine candidate in mice immunized through homologous or heterologous prime-boost regimens with the Ad5 vectored Ebola vaccine were assessed by ELISA and ELISPOT assays. The data showed that mice in groups primed with rLS/EB-GP and boosted with Ad5-MakGP (NDV+Ad5) or reversed Ad5-MakGP prime and rLS/EB-GP boost (Ad5+NDV) elicited more potent EBOV GP-specific antibody and cellular immune responses than homologous regimens alone. The most robust EBOV GP-specific antibody and T-cell responses were detected in the Ad5-MakGP primed, and rLS/EB-GP boosted (Ad5+NDV) mice. These results suggested that the Ad5 prime-NDV boost regimen is more effective in stimulating EBOV specific immunities than homologous regimens alone, indicating the potential boosting ability of the NDV vector in human vaccine use.