Continuous emergence of SARS-CoV-2 variants which cause breakthrough infection from the immunity induced by current spike protein-based COVID-19 vaccines highlights the need for new generations of vaccines that will induce long-lasting immunity against a wide range of the variants. To this end, we investigated the protective efficacy of the recombinant COVID-19 vaccine candidates based on a novel VACV ACAM2000 platform, in which an immunoregulatory gene, E3L, was deleted and both the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens were expressed.
Polycation treatment of L cell monolayers affected plaquing efficiency of both the r+ and r variants of the encephalomyocarditis virus. Plaque formation by r+ variant was decreased markedly by three structurally different types of synthetic basic polymers, diethylaminoethyl dextran, hexadimethrene (polybrene), and basic polyamino acids. In contrast, these same substances increased substantially the number of plaques formed by the r variant. The effect on the two variants was observed when polycations were applied to the cells before or simultaneously with the introduction of virus. The molar concentration and size of the polymer proved important. Thus, basic polyamino acids of low molecular weight were significantly more inhibitory for the r+ variant than were those of high molecular weight. On the other hand, plaquing efficiency of the r variant was increased by relatively large polyamino acids, but not by polymers of small size. Basic polyamino acids inhibited r+ plaque formation to a greater degree at low than at high pH values. However, plaquing efficiency of the r variant in polycation-treated cultures was not affected by changes in pH. Basic polymers appear to bind to cell membranes and affect either attachment or uptake of the viruses. The evidence suggests that the substances influence by different mechanisms the interaction of the r+ and r variants with cells.
The high transmissibility of SARS-CoV-2 is an important viral factor defining the coronavirus disease 2019 (COVID-19) pandemic. To transmit efficiently, SARS-CoV-2 must be capable of disarming the innate immune response of its host efficiently.
SUMMARYIncreasing cases of SARS-CoV-2 breakthrough infections from immunization with predominantly spike protein based COVID-19 vaccines highlight the need for alternative vaccines using different platforms and/or antigens. In this study, we expressed SARS-CoV-2 spike and nucleocapsid proteins in a novel vaccinia virus ACAM2000 platform (rACAM2000). Following a single intramuscular immunization, the rACAM2000 co-expressing the spike and nucleocapsid proteins induced significantly improved protection against SARS-CoV-2 challenge in comparison to rACAM2000 expressing the individual proteins in a hamster model, as shown by reduced weight loss and quicker recovery time. The protection was associated with reduced viral loads, increased neutralizing antibody titre and reduced neutrophil-to-lymphocyte ratio. Thus, our study demonstrates that the rACAM2000 expressing a combination of the spike and nucleocapsid antigens is a promising COVID-19 vaccine candidate and further studies will investigate if the rACAM2000 vaccine candidate can induce a long lasting immunity against infection of SARS-CoV-2 variants of concern.
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