Safety and immunogenicity of intramuscular, single-dose V590 (rVSV-SARS-CoV-2 Vaccine) in healthy adults: Results from a phase 1 randomised, double-blind, placebo-controlled, dose-ranging trial

Preclinical immunogenicity and efficacy of a candidate COVID-19 vaccine based on a vesicular stomatitis virus-SARS-CoV-2 chimera

“…Some of the preclinical data presented here provide useful context for considering the basis for the low immunogenicity of the single IM dose of VSV∆G-SARS-CoV-2 #9 observed in the phase 1 clinical trial. 18 Yet, more importantly, the research described here, as well as by others 50 , 86 also provides encouraging data to support the development and further evaluation of an intranasal VSV∆G-SARS-CoV-2 vaccine that could help prevent upper respiratory tract infection by SARS-CoV-2 and reduce transmission from asymptomatic infected individuals.…”

“… 72 However, due to the urgent need to develop an effective COVID-19 vaccine when this programme was initiated, we expedited the development of VSV∆G-SARS-CoV-2 for IM injection by making use of the substantial nonclinical and clinical data associated with the ebolavirus Zaire vaccine ERVEBO®, which is delivered by the IM route. 14 , 15 , 85 Moreover, advancing a vaccine for administration by standard IM injection was well supported by immunogenicity and efficacy data produced here using the hamster model, as well as a full nonclinical safety assessment that was completed before advancing to human trials (unpublished data); thus, VSV∆G-SARS-CoV-2 #9 (called V590) was advanced and evaluated in a phase 1 clinical trial, 18 which showed that a single IM injection with V590 was safe but not sufficiently immunogenic to continue with the product development path based on a vaccine for IM injection. Some of the preclinical data presented here provide useful context for considering the basis for the low immunogenicity of the single IM dose of VSV∆G-SARS-CoV-2 #9 observed in the phase 1 clinical trial.…”

“…The VSV∆G-SARS-CoV-2 #9 constellation of mutations was stable during the manufacturing of vaccine material to support the phase 1 trial. 18 …”

“…Accordingly, administration of a single IM dose of VSV∆G-SARS-CoV-2 #9 (V590) was evaluated in a phase 1 clinical trial. 18 …”

“…Although we had encouraging preclinical data from studies in cotton rats and hamsters supporting use of a single IM injection of VSV∆G-SARS-CoV-2, these positive results failed to translate to vaccine responses observed in humans. 18 The reason for the conflicting results between rodents and humans is speculative and is yet to be fully defined; however, as mentioned above, our cotton rat data ( Figure 2 ) suggested that it was possible to induce humoral immune responses in rodents by IM injection in the absence of significant infection and replication primarily through immune responses induced by the regular arrays of Spikes on the input VSV∆G-SARS-CoV-2 virions ( Figure 1 e) 91 and perhaps this is augmented by virion components interacting with viral sensors such as Spike binding to toll-like receptor 4. 92 The possibility that IM injection was immunogenic in rodents without substantial virus infection also may be extended to our hamster data ( Figures 3 and 5 ), because skeletal muscle tissue is not a rich source of cells expressing ACE2 receptors 74 , 93 that could support infection.…”