The rVSV-EBOV vaccine provides limited cross-protection against Sudan virus in guinea pigs

Abstract

Recombinant vesicular stomatitis viruses (rVSVs) engineered to express heterologous viral glycoproteins have proven to be remarkably effective vaccines. Indeed, rVSV-EBOV, which expresses the Ebola virus (EBOV) glycoprotein, recently received clinical approval in the United States and Europe for its ability to prevent EBOV disease. Analogous rVSV vaccines expressing glycoproteins of different human-pathogenic filoviruses have also demonstrated efficacy in pre-clinical evaluations, yet these vaccines have not progressed far beyond research laboratories. In the wake of the most recent outbreak of Sudan virus (SUDV) in Uganda, the need for proven countermeasures was made even more acute. Here we demonstrate that an rVSV-based vaccine expressing the SUDV glycoprotein (rVSV-SUDV) generates a potent humoral immune response that protects guinea pigs from SUDV disease and death. Although the cross-protection generated by rVSV vaccines for different filoviruses is thought to be limited, we wondered whether rVSV-EBOV might also provide protection against SUDV, which is closely related to EBOV. Surprisingly, nearly 60% of guinea pigs that were vaccinated with rVSV-EBOV and challenged with SUDV survived, suggesting that rVSV-EBOV offers limited protection against SUDV, at least in the guinea pig model. These results were confirmed by a back-challenge experiment in which animals that had been vaccinated with rVSV-EBOV and survived EBOV challenge were inoculated with SUDV and survived. Whether these data are applicable to efficacy in humans is unknown, and they should therefore be interpreted cautiously. Nevertheless, this study confirms the potency of the rVSV-SUDV vaccine and highlights the potential for rVSV-EBOV to elicit a cross-protective immune response.

Protective Efficacy of Lyophilized Vesicular Stomatitis Virus–Based Vaccines in Animal Model

“…Animals immunized with Ly-VSV∆G/EBOVGP vaccine all had EBOV-specific ELISA titers > 1:6,400. Although those animals were not challenged with EBOV to assess the in vivo protective efficacy of the Ly-VSV∆G/EBOVGP vaccine, their antibody responses were consistent with a predicted protective response on the basis of findings from other studies, including studies using a similar EBOV guinea pig model ( 9 , 10 ). Instead, we used Ly-VSV∆G/EBOVGP–immunized animals as sham-vaccinated control animals in the lethal LASV challenge experiment to control for nonspecific immunity associated with the LST stabilizer formulation.…”

“…We evaluated vaccine-induced humoral immune responses in serum samples collected immediately before virus challenge (28 days postimmunization) by using LASV and EBOV glycoprotein-specific ELISAs, as previously described ( 8 , 9 ). Animals immunized with Ly-VSV∆G/EBOVGP vaccine all had EBOV-specific ELISA titers > 1:6,400.…”

Single dose recombinant VSV based vaccine elicits robust and durable neutralizing antibody against Hantaan virus

“…The pre-existing immunity against the vector also poses other obstacles to the clinical use of these candidates 28 . rVSV is an ideal vaccine platform that can easily incorporate other viral GPs and has been investigated extensively 16 , 29 – 31 . The most evident example is Merck’s certified ERVEBO, which is a replication-competent VSV that encodes the EBOV glycoprotein and shows the ability to induce a humoral immune response 32 .…”

Could SARS-CoV-1 Vaccines in the Pipeline Have Contributed to Fighting the COVID-19 Pandemic? Lessons for the Next Coronavirus Plague

“…In a very recent article, Canadian and U.S. researchers tested the heterologous immunity hypothesis with two Ebolaviruses: Sudan and Zaire. In the guinea pig model, the authors demonstrated that 60% of animals vaccinated with a recombinant vesicular stomatitis virus (rVSV) engineered to express heterologous Zaire ebolavirus viral glycoprotein survived the challenge with Sudan ebolavirus [13]. These results indicated limited but relevant cross-protection in the rodent model.…”