Inovio Pharmaceuticals Inc (INO)

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10/14/21: Nature Comms: INO-4800 DNA vaccine induces neutralizing antibodies and T cell activity against global SARS-CoV-2 variants.
INO-4800 generates robust neutralizing antibodies against P.1 at levels comparable to the Wuhan strain. Despite similarities in the RBD of P.1 and B.1.351, studies have reported a reduced impact in neutralization against P.1, compared to B.1.35118,19. In sera from individuals who received the SARS-CoV-2 mRNA-1273 or the BNT162b2 vaccines, there was a 2.8 and 2.2-fold reduction in neutralization against P.1, compared to 8.6 and 6.5-fold for B.1.351, respectively18. The lower resistance to neutralization conferred by the P.1 variant suggests that changes outside the RBD, especially in the NTD, where P.1 and B.1.351 acquired and accumulated different mutations, may play a role in neutralization. INO-4800 induces cross-reactive T cell responses against B.1.1.7, B.1.351, and P.1 variants that are comparable to the Wuhan strain. Taken together, these data demonstrate maintenance of one or both cellular and humoral arms of the immune response against emerging SARS-CoV-2 variants for the INO-4800 vaccine, which will likely be critical factors to impact the ongoing COVID-19 pandemic.

We performed a SARS-CoV-2 pseudovirus neutralization assay using sera collected from thirteen subjects two weeks after administration of a third dose of 0.5, 1, or 2?mg of INO-4800 (Supplementary Table 1). Neutralizing activity was detected against Wuhan and the emerging variants in all serum samples tested (Fig. 1b). The mean ID50 titers for the Wuhan, B.1.1.7, B.1.351, and P.1. were 643, 295, 105, and 664, respectively (Supplementary Tables 1 and 2). Compared to Wuhan, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between Wuhan and the P.1 variant. These results are consistent with other recent studies, which have demonstrated a significant reduction in neutralizing activity in vaccinated individuals towards the B.1.351 (≥6-fold reduction), while the B.1.1.7 lineage has demonstrated a reduced activity of two-fold or less4,7,8,9,17. Strikingly, while the P.1 strain presents with similar RBD mutations as B.1.351, we did not observe any reduction in neutralizing activity compared to the Wuhan strain in INO-4800 vaccinated individuals.

Received
13 April 2021

Accepted
06 July 2021

Published
14 October 2021

https://www.nature.com/articles/s41541-021-00384-7