In a study published in Molecular Therapy researchers from KTH among others have generated several different DNA vaccines selectively activating neutralizing antibodies (Nabs) and/or T cells and used them in different animal models to study their individual roles in the protection against severe SARS-CoV-2.

SARS-CoV-2 infection or vaccination induces Nabs that can prevent infection for a short period and is highly effective in preventing hospitalization or death for an extended time. The ability of the virus to mutate however poses a challenge as mutations in surface-exposed protein regions, which are usually the epitopic regions among humans, can escape Nabs. T cells that also target more conserved genes, such as membrane (M) and nucleoprotein (N), can on the other hand be maintained for very long periods of time and also be cross-reactive to new SARS coronavirus and even animal SARS-like coronaviruses. Therefore, vaccines that induced NAbs, T cells, or both, in different challenge models was designed and evaluated in this study.

The results show that high levels of NAbs neutralized several coronavirus variants in vitro, but when using T cell inducing vaccines pre-existing T cells resulted in anamnestic antibody responses and a better control of SARS-CoV-2 replication. However, in the absence of Nabs this viral control may result in more pronounced clinical signs and histological damage and therefore good protection against disease requires both NAbs and cross-reactive T cells.

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