Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens. ### Competing Interest Statement A.P., E.L.R., E.P., E.N.G., M.P., D.F., F.I.Z, A.K., declare no competing interests. J.N.W., B.S., K.S., I.M., Z.E., A.D., D.E., A.G., V.M.A., J.J.K., L.M.H., S.J.R., T.R.F.S., K.E.B. are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. D.B.W. discloses the following paid associations with commercial partners: GeneOne (Consultant), Geneos (Advisory Board), Astrazeneca (Advisory Board, Speaker), Inovio (BOD, SRA, Stock), Pfizer (Speaker), Merck (Speaker), Sanofi (Advisory Board), BBI (Advisory Board).