Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior immune response to SARS-CoV-2

Abstract

Immunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular immunization resulted in high titers of spike-specific neutralizing antibodies. The vaccinated animals were fully protected following infection with a lethal dose of SARS-CoV-2-SD614G via the nasal route, and partially protected if challenged with the SARS-CoV-2Delta variant. While dissemination of the challenge virus to the brain was completely inhibited, replication in the lung with consequent lung pathology was not entirely controlled. Thus, intramuscular immunization was clearly enhanced by trans-complementation of the VSV-vectored vaccines by the VSV glycoprotein and led to protection from COVID-19, although not achieving sterilizing immunity.

Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study

“…SARS-CoV-2 pseudovirus neutralisation assay against the SARS-CoV-2 parental strain was performed as described using a green fluorescent protein reporter-based pseudotyped virus with a vesicular stomatitis virus backbone coated with SARS-CoV-2 spike protein. 12 Values above 23 BAU/mL and above a titre of 8 were considered positive for IgG and neutralising antibodies, respectively. Of all samples, 15% were randomly selected and assessed for T-cell activation; enzyme-linked immune absorbent spot was used to measure antigen-specific T cells that secrete IFN-γ.…”

Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation

“…Viral titers were expressed as 50% tissue culture infective dose per ml (TCID 50 /ml). Vesicular stomatitis virus (VSV) encoding green fluorescent protein (GFP) and expressing the C-terminally truncated spike protein of SARS-CoV-2 (VSV*ΔG-S Δ21 ) was previously described [ 36 ].…”

Effectiveness of VSV vectored SARS-CoV-2 spike when administered through intranasal, intramuscular or a combination of both

“…Since the beginning of the pandemic, different VSV based vaccine vectors expressing spike protein (full length or truncated) have been studied and shown to protect hamsters and mice from SARS-CoV-2 infection by inducing a strong immunity 29 – 35 . Two of these VSV based vaccine vectors expressing spike protein led to clinical trials.…”

“…The potential that minimal expression of ACE2, the cellular receptor for SARS-CoV-2 spike, is found on the surface of skeletal muscle cells 19 , 21 may greatly reduce the efficiency of a VSV-SARS-CoV-2 spike vaccine such as V590 when administered intramuscularly. A recent study by Taddeo et al 29 showed an optimized and enhanced IM route of VSV based viral vector spike vaccination using trans-complemented with the VSV-G glycoprotein. VSV-G is known to have broad tissue tropism.…”