N protein based vaccine against SARS-CoV-2 produces a strong T cell immune response to N Protein of novel strains

Abstract

The second generation COVID-19 vaccines should produce the long-term protective immune response to the existing and novel strains of SARS-CoV-2. The Convacell® vaccine was designed to produce such immune response by using N protein as an antigen. N-protein is not susceptible to fast accumulation of mutations and is highly homologous to nucleocapsid proteins of other β-coronaviruses. The study was aimed to perform in vitro assessment of the Convacell® vaccine ability to produce immune response to the Wuhan, Delta, and Omicron strains. Mononuclear cells of vaccinated volunteers and survivors were subjected to N protein stimulation. After that specific activation of the cells was assessed by flow cytometry. The results showed that a sibstantial percentage of CD4 and CD8 cells produced IFNγ and IL2 in response to stimulation. No significant reduction of the response to strains Delta and Omicron compared to the Wuhan strain was revealed. The findings support the direction of the N protein based vaccine design towards creation of the universal vaccine.

Safety and Immunogenicity of the Convacell® Recombinant N Protein COVID-19 Vaccine

“…Notably, considering that the main circulating variant of SARS-CoV-2 during the course of the study was Omicron, and that Convacell ® is based on the N protein of the Wuhan variant, the conclusions above can be extended to suggest that Convacell ® generates an immune response that is cross-specific against the Omicron and the Wuhan variants of the virus. This is fully congruous with the results of our earlier study [ 15 ]. Phase IIb contained no placebo control groups, and therefore no conclusion can be reached about the putative effectiveness of Convacell ® based on the COVID incidence observed in that phase.…”

“…The phenotyping of activated PBMCs in response to stimulation with the N-protein-derived peptides in the peripheral blood of vaccinated volunteers in phase II revealed a statistically significant increase from approximately 0.5 activated cells per 10,000 to approximately 2 activated cells per 10,000, compared to time point 0, only for the CD4 + IFNγ + T-cells of the single vaccination group, on days 180–350. This is indicative of a weaker response than that observed in the results of Convacell’s ® preclinical evaluations, where we confirmed that Convacell ® induces strong cellular immune response in non-human primates and mice [ 5 , 15 ]. The phase IIb findings indicated a significant and rapid rise from day 0 to day 42 in the levels of circulating N-specific IFNγ-producing PBMCs in both single vaccination and double vaccination groups, regardless of volunteer age.…”

“…A dose of Convacell ® contains 50 μg of protein N with the Wuhan SARS-CoV-2 variant sequence. The N protein is highly conserved and less prone to accumulate mutations than the commonly used in vaccines spike (S) protein [ 9 , 10 , 11 , 12 , 13 , 14 ], which allows Convacell ® to generate long-lasting [ 5 ] and broadly acting [ 15 ] immune responses. The N protein is also abundantly expressed in cells after infection [ 16 , 17 ] and exposed on the infected cells membranes [ 18 , 19 ], ensuring that infected cells are highly likely to be targeted by N-specific immune responses.…”

Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell®

“…The usage of conservative N protein as an antigen allows Convacell ® to be considered as a candidate pan-sarbecovirus vaccine. It may be useful in the fight against the COVID-19 pandemic despite the emergence of new virus variants [77], and accordingly clinical trials with Convacell ® have been initiated [58].…”

N-protein vaccine Convacell® is effective against COVID-19: phase 3, randomized, double-blind, placebo-controlled clinical trial

“…The usage of the internal N protein as the main antigen in Convacell® confers on it a number of advantages. The N protein is notably conservative (7,8,(21)(22)(23)(24), which confers onto Convacell®-generated immune responses both longevity (5) and broad cross-reactivity among SARS-CoV-2 variants (25). The internal nature of the N protein in mature virions does not negatively affect Convacell®'s protectivity, as the N protein is highly expressed in infected cells (26,27) and exposed on their membranes (28,29), which allows such cells to be targeted and eliminated by cytotoxic T-cell (30)(31)(32) and natural killer (NK) cell action (33)(34)(35).…”