Discussion
redness, headaches, head aches, fatigue, pain, muscle pain, RBD
EVENTS
Vaccination with PTX-COVID19-B in 45 subjects of ages between 18- and 64-year-old did not result in any overt safety signal. Local reactions were mild after the first vaccine dose in general. Moderate to severe local pain was observed in a small number of participants (Cohorts 1 6%, and 26.7% for Cohorts 2 and 3). Similarly, systemic reactions were mild for most of the participants. Moderate headaches were observed in 6.7% of Cohort 1 and 13.3% of Cohort 2 participants. Moderate muscle pain was reported in 6.7% of Cohort 3 and 13.3% of Cohort 1 and severe pain was reported in 6.7% of Cohort 2.After the second dose moderate pain at the injection site was similar to the first vaccine injection (13%, 0% and 26.7% for Cohorts 1, 2 and 3, respectively). However, moderate, and severe redness was observed in participants of Cohort 3 (33%). Also, moderate head aches and fatigue increase in Cohort 3–26% and 33% respectively whereas Cohort 2 showed systemic events only in 7.1% of the participants. These post second dose AE results let us to conclude that 16 μg and 40 μg would be preferred doses for vaccine development. Since the study is small, safety needs to be confirmed in follow up clinical trials with a larger number of participantsPTX-COVID19-B induced antibody titers against RBD and Spike remain high and above the values of COVID-19 convalescence serum over a period of 6 months (day 180) after initial vaccination, especially in the 40 μg and 100 μg dose cohorts, indicating a durable systemic antibody response.Neutralizing antibody was observed in 100% of the vaccinated participants after the first immunization at day 28 regardless of the dose level. We speculate that this early induction of neutralizing antibody may be beneficial for vaccinees since it may provide early protection against SARS-CoV-2.The neutralization serum activity post second immunization, determined using the Pseudovirus assay, was lower for the VOCs compared to the G614 strain. Fold titer reduction against Alpha was 2, against Delta was 3 in all three dose cohorts and against Beta was 4 in the 40 μg and 100 μg cohort. Some studies report similar findings with individuals vaccinated with approved mRNA vaccines, where the fold reduction against Alpha is 2, against Delta is 3–4 and more than 10 for Beta variantsStudies proposing predictive models of COVID19 vaccine efficacy using data from approved vaccines, indicate that neutralizing antibody titers above twofold the value of HCS are predictive of over 80% efficacy protection against SARS-CoV2 ancestral strain infectionThe 40-µg dose was selected to progress into a Phase 2 clinical trial, because it had the right balance between the immune response and satisfactory reactogenicity profile.Critical limitations of this trial include a small study population and limited ethnic diversity as compared with the general population. Additionally, as a Phase 1 safety trial, the study population did not include those at increased risk of severe illness from COVID-19, including older adults and immunocompromised individuals that may mount a weaker immune response to vaccination.Although several COVID-19 vaccines have been approved globally (most under emergency or interim use), issues remain with supply and delivery of vaccines to combat emerging variants. Additional safe, effective, and easily deployable SARS-CoV-2 vaccines are needed to meet the challenge for global immunization required to end the pandemic. Based on the reported results, PTX-COVID19-B vaccine is a promising candidate that warrants testing in the next phase of trials. A Phase 2 comparator trial of PTX-COVID19-B and Comirnaty in 525 healthy adults with the 40-µg dose has been performed and data is being analyzed for a future report. T cell responses were evaluated in a significant number of participants of the Phase 2 trial to complete the immune response profile of the vaccine.The sera from subjects vaccinated with PTX-COVID19-B did not cross neutralize Omicron Spike expressing pseudovirus (data not shown). These results were expected since Omicron Spike from the new VOC differ in more than 30 amino acids from D614G Spike. Based on the performance of the mRNA and LNP of PTX-COVID19-B, future booster vaccine development is planned with updated Spike versions of circulating strains.