A SARS-CoV-2 vaccine designed for manufacturability results in unexpected potency and non-waning humoral response

Abstract Despite the availability of a number of COVID-19 vaccines, there still exists a large unmet need for vaccines which provide durable immunity and protection against emerging SARS-CoV-2 variants, and for vaccines with lower manufacturing costs and reduced logistical requirements for distribution. We have developed a novel protein component vaccine candidate, MT-001, based on a fragment of the SARS-CoV-2 spike protein surrounding the receptor binding domain (RBD). Mice vaccinated with a 2-dose prime-boost regimen of MT-001 adjuvanted with alum and CpG exhibited peak anti-spike IgG ELISA titers comparable to those reported for mRNA vaccines from Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273), and, in contrast to the mRNA vaccines, these titers were found to be durable with midpoint GMTs in the range of 105 – 106 up to 12 months post-vaccination. Syrian golden hamsters vaccinated with a similar 2-dose regimen of MT-001 exhibited undetectable levels of SARS-CoV-2 in lung tissue four days after intranasal challenge with SARS-CoV-2/US-WA1. In mice, the results showed an increased breadth of the response, with significant neutralization titers against the Omicron BA.1 variant at this timepoint. These attributes make MT-001 a compelling candidate for a next-generation COVID-19 vaccine. MT-001 could be particularly valuable as an annual booster for individuals with diverse histories of vaccination, SARS-CoV-2 infection, and/or predispositions resulting in an immunocompromised state. MT-001 was designed for manufacturability and ease of distribution, and we demonstrate that these attributes are not inconsistent with a highly immunogenic vaccine that confers durable and broad immunity to SARS-CoV-2 and its emerging variants. Supported by grants from Rutgers University CCRP2 and the New Jersey Health Foundation. In-kind support from CEPI is also gratefully acknowledged.