Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi, Anahita; Dahlke, Christine; Addo, Marylyn M.

V920 trial numbers adapted from Monath et al. NIAID = National Institute of Allergy and Infectious Diseases a change of this policy, offering pregnant and lactating women as well as children under the age of 12 months who are contacts of identified EVD cases the vaccine as of June 15 th 46,47 which is not only vital for the protection of this population, but is also an opportunity to generate data on vaccine safety and efficacy in this group and will be of great value in future outbreaks. As EVD outbreaks occur in a population with high HIV incidence rates, it is all the more important to evaluate how safe the vaccine is in immunocompromised individuals. VSV-EBOV was reported to be tolerable in severely immunocompromised NOD-SCID mice 48 and was consecutively tested in a simian-human immunodeficiency (SHIV) model. SHIV infected macaques did not develop overt symptoms such as fever after vaccination with 1 × 10 7 PFU of VSV-EBOV, a dosage previously shown to be protective in NHPs. The immunogenicity of the vaccine was limited, and EBOV-GPspecific antibodies could not be detected prior to challenge. When challenged with a lethal dose of EBOV 31 days postvaccination (p.v.), 4/6 of vaccinated animals showed clinical signs of illness and two of them ultimately died. These two animals had been most affected by SHIV as they displayed the highest SHIV viremia and had the lowest CD4+ T cell counts in the group. Also, unlike the survivors, they did not show VSV viremia after vaccination. 49 This study underlines the need for a further assessment of VSV-EBOV in immunocompromised individuals and probably for adapting vaccine dosage and schedule. One phase II trial of VSV-EBOV to date has included a small subgroup of 22 HIV-positive individuals: no SAE was reported in HIV-positive participants within one month of vaccination, but immunogenicity as measured by antibody responses was found to be lower as compared to HIV-negative individuals. 34 To generate data in a larger cohort, the ongoing ACHIV phase II trial is specifically examining the safety and immunogenicity of VSV-EBOV in an estimated 200 HIV-positive individuals.