Heterologous prime-boost regimens with HAdV-5 and NDV vectors elicit stronger immune responses to Ebola virus than homologous regimens in mice

Zhao, Wei; Zhang, Peng; Bai, Shuang; Lv, Min; Wang, Jian; Chen, Weixin; Yu, Qingzhong; Wu, Jiang

The 2014 Ebola outbreak in West Africa resulted in more than 11,000 deaths, highlighting the need for a vaccine. A phase I clinical trial of a human adenovirus type 5 vector-based Ebola virus (EBOV) vaccine (HAdV-5-MakGP) showed that a homologous prime-boost regimen with HAdV-5 vaccine elicited a robust humoral response but a weak cellular immune response. Due to pre-existing anti-vector immunity, boosting with the same vaccine did not increase the magnitude of the cellular immune response, which contributes significantly to protection against EBOV infection. Here, we generated a recombinant Newcastle disease virus (NDV), based on the LaSota vaccine strain, expressing the GP protein of the EBOV variant Makona (rLS/EB-GP) using reverse genetics technology. The humoral and cellular immune responses to this vaccine candidate in mice immunized using a homologous prime-boost regimen or a heterologous prime-boost regimen with the HAdV-5-vectored Ebola vaccine were assessed using ELISA and ELISPOT assays. The ELISA and ELISPOT results showed that mice primed with rLS/EB-GP and boosted with HAdV-5-MakGP (NDV+HAdV-5) or, reversed, primed with HAdV-5-MakGP and boosted with rLS/EB-GP (HAdV-5+NDV) exhibited more-potent EBOV GP-specific antibody and cellular immune responses than those receiving the same vaccine twice. The most robust EBOV GP-specific antibody and T-cell responses were detected in the HAdV-5-MakGP-primed and rLS/EB-GP-boosted (HAdV-5+NDV) mice. These results suggest that the HAdV-5 prime-NDV boost regimen is more effective in stimulating EBOV-specific immunity than homologous regimens alone, indicating the potential boosting ability of the NDV vector in human vaccine use.