Characterization of a Species E Adenovirus Vector as a Zika virus vaccine

Abstract

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to characterize the T-cell biased immune response observed in Ad4 immunized mice. Vaccination of BALB/c mice resulted in immune correlates similar to C57BL/6 mice, confirming that this response is not mouse strain-specific. Vaccination with an Ad4 expressing an influenza hemagglutinin (HA) protein resulted in anti-HA T-cell responses without the development of significant anti-HA antibodies, indicating this unique response is specific to the Ad4 serotype rather than the transgene expressed. Co-administration of a UV inactivated Ad4 vector with the Ad5-prM-E vaccine led to a significant reduction in anti-ZIKV antibody development suggesting that this serotype-specific immune profile is capsid-dependent. These results highlight the serotype-specific immune profiles elicited by different Adenovirus vector types and emphasize the importance of continued characterization of these alternative Ad serotypes.

Prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

“…This difference may be caused by the different serotype of adenovirus vectors (Sad23L and Ad49L were classified in species E and D of adenoviruses, respectively) [7], actual antigen or animals used in the study. The discrepancy was previously observed for the stronger T cell response but weaker antibody reactivity from Ad4 and AdC68 vectored vaccines [34,35]. The reason might be explained for that Ad49L induced the higher type I interferon (IFN)…”

Current Progress in the Development of Zika Virus Vaccines

“…Surprisingly, ELISA and plaque reduction neutralization tests showed negligible levels of anti-ZIKV antibodies after Ad4-prM-E-vaccination in C57BL/6 mice, suggesting that Ad4-prM-E vaccination induces only T-cell responses, whereas Ad5-prM-E vaccination induced both anti-ZIKV antibody and T-cell response [39]. Interestingly, coadministration of UV-inactivated Ad4 vector with Ad5-prM-E vaccine led to significant reduction in CTL and overall T-cell responses, compared to Ad5-prM-E alone [40], highlighting the differences in serotypespecific immunity induced by adenovirus vectors.…”

Novel approaches for vaccine development

“…The rapid and scalable development potential of Ad vector-based vaccines have also made them well-suited for outbreak scenarios when rapid vaccine development and widespread distribution are critical. Consequently, adenoviral vaccines have been developed for outbreak viruses such as Ebola (Tapia et al, 2020) and Zika (Abbink et al, 2016;Bullard et al, 2020;Larocca et al, 2019).…”