Abstract
Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and mid-income countries (LMICs) is still suboptimal. Second generation vaccines that are universally affordable and induce systemic and mucosal immunity are needed. Here we performed an extended safety and immunogenicity analysis of a second-generation SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing a pre-fusion stabilized version of the spike protein (NDV-HXP-S) administered intranasally (IN), intramuscularly (IM), or IN followed by IM in Sprague Dawley rats. Local reactogenicity, systemic toxicity, and post-mortem histopathology were assessed after the vaccine administration, with no indication of severe local or systemic reactions. Immunogenicity studies showed that the three vaccination regimens tested elicited high antibody titers against the wild type SARS-CoV-2 spike protein and the NDV vector. Moreover, high antibody titers were induced against the spike of B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants of concern (VOCs). Importantly, robust levels of serum antibodies with neutralizing activity against the authentic SARS-CoV-2 USA‐WA1/2020 isolate were detected after the boost. Overall, our study expands the pre-clinical safety and immunogenicity characterization of NDV-HXP-S and reinforces previous findings in other animal models about its high immunogenicity. Clinical testing of this vaccination approach is ongoing in different countries including Thailand, Vietnam, Brazil and Mexico.
Highlights
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted over 250 million people worldwide and has caused the death of at least 5 million people (WHO, 2021)
We used the previously designed NDV-HXP-S vaccine based on the NDV LaSota strain expressing a chimeric protein consisting of the spike (S) ectodomain from SARS-CoV-2 and the transmembrane domain and cytoplasmic tail (TM/CT) of the NDV fusion protein [27, 30]
The resulting virus comprising the vaccine was expanded in embryonated eggs in the Vaccine and Cell Therapy Laboratory (VCTL) at the Icahn School of Medicine at Mount Sinai
Summary
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted over 250 million people worldwide and has caused the death of at least 5 million people (WHO, 2021). In the United States three vaccines have been authorized to prevent the coronavirus disease 2019 (COVID-19): two mRNA-based approaches, including BNT162b2 (from Pfizer) and mRNA-1273 (from Moderna), and the viral vector-based approach JNJ78436735 (from Johnson & Johnson) [2,3,4]. BNT162b2 was fully licensed by the U.S Food and Drug Administration as the first vaccine to prevent COVID-19 [5]. The generation of these vaccines in such a record time and their rollout in the population - with an initial Emergency Use Authorization (EUA) - represents a milestone for vaccine development and science in general. Mechanisms of vaccine-induced protection involve the induction of neutralizing antibodies, mostly directed against the viral spike protein [14, 15], as well as cellular responses [16, 17]
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