Phase 1 trial of COVID-19 PTXCOVID19-B vaccine

By Shanet Susan AlexReviewed by Aimee MolineuxMay 12 2022

A recent phase 1 study posted to the medRxiv* preprint server demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PTXCOVID19-B vaccine was a promising SARS-CoV-2 vaccine option.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

The SARS-CoV-2 global pandemic, which began in 2019, is still affecting nations with inadequate Coronavirus disease 2019 (COVID-19) vaccination access. 

Providence Therapeutics Holdings, Inc. (PT) devised a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine, PTX-COVID19-B, that consisted of a lipid nanoparticle-containing altered mRNA encoding full-length spike (S) protein harboring glycine in position 614 (G614). Further, due to the lack of proline-proline mutation at the 986-987 position present in other SARS-CoV-2 vaccines, PTX-COVID19-B might have a comparatively higher potency. PTX-COVID19-B was found to be safe, significantly immunogenic, and effectively protected animals from COVID-19 in preclinical investigations. Health Canada approved clinical studies of PTX-COVID19-B in December 2020 based on preclinical data.

About the study

The present phase 1 randomized, placebo-controlled, observer-blinded, ascending dose trial assessed the tolerability, immunogenicity, and safety of PTX-COVID19-B two-dose vaccination among healthy seronegative subjects. The research was conducted in Canada and started in January 2021, and participant recruitment finished in April 2021. All included participants tested SARS-CoV-2-seronegative and were negative for reverse transcription-polymerase chain reaction (RT-PCR), displaying no indication for recent incidence of COVID-19 or other viral respiratory illnesses.

Individuals aged 18 to 64 years were vaccinated with two shots of the PTX-COVID19-B vaccine intramuscularly with a four-week interval using 100 μg, 40 μg, or 16 μg doses. The study volunteers were divided into three cohorts based on the vaccine dose consisting of 20 participants each, and five subjects in each group were injected with a placebo (sodium chloride 0.9%). The safety database was secured, and data up to day 42 following the first shot in May 2021 were analyzed. Moreover, immunological data were available until week 26, i.e., day 180.

Results and discussions

The study results illustrated that in 18- to 64-year-old subjects, the SARS-CoV-2 PTX-COVID19-B vaccination demonstrated a safe profile. Most adverse events following the PTX-COVID19-B vaccination were self-resolving, transient, and mild to moderate. While the most often reported systemic adverse reaction was headaches, the frequent local adverse event was pain. Local and systemic effects were mild following the initial vaccine dose, and only a small percentage of subjects experienced moderate reactions after the second shot. So far, the PTX-COVID19-B vaccination has caused fewer adverse reactions than currently authorized COVID-19 vaccines. 

All subjects seroconverted after the initial PTX-COVID19-B vaccination, generating higher concentrations of neutralizing, anti-receptor-binding-domain (RBD), and anti-S antibodies. Further, these neutralizing antibodies targeted the SARS-CoV-2 ancestral strain and the Delta, Alpha, and Beta variants of concern (VOCs), in a dose-reliant manner, with levels increasing by 10- to 20-fold after the second shot. 

After the initial vaccination on day 28, neutralizing antibodies were found in 100% of the immunized subjects, independent of the dose used, superior to the seroconversion rate of neutralizing antibodies associated with the Pfizer and Moderna COVID-19 mRNA vaccines in their phase 1 and 2 clinical studies. This early development of neutralizing antibodies might benefit vaccinees by providing immediate immunity against SARS-CoV-2 following vaccination.

Antibody titers for the 100 μg and 40 μg dose groups were elevated than the SARS-CoV-2 convalescence serum at roughly six months, i.e., day 180, following vaccination, suggesting more lasting protection than existing mRNA vaccines. Furthermore, the concentrations of neutralizing antibodies evoked by PTX-COVID19-B targeting the SARS-CoV-2 ancestral strain and VOCs were similar to several existing mRNA vaccines and more than the titers considered protective, implying that PTX-COVID19-B was as effective as the currently authorized COVID-19 mRNA vaccines.

PTX-COVID19-B exhibited a robust immunogenic response and was safe and well-tolerated at all doses tested. Notably, the 40μg dose had fewer adverse events than the 100μg dose, suggesting that it should be studied further.

Conclusions

According to the findings of this phase 1 study, the PTX-COVID19-B vaccine was a potential SARS-CoV-2 vaccine candidate and should be tested in the further stages of clinical trials. Follow-up clinical studies with a broader range of subjects were needed to establish the enhanced safety of the PTX-COVID19-B vaccine.

The 40 μg dose of PTX-COVID19-B has been chosen for Phase 2 clinical studies because of its tolerability, safety, and immunogenicity, particularly the neutralizing antibody response against SARS-CoV-2 VOCs. The authors mentioned that a Phase 2 study for a 40 μg dose of the vaccine encompassing 525 healthy adults is currently underway. In 2022, a comprehensive Phase 3 experiment of the PTX-COVID19-B vaccine will be conducted. Moreover, the efficacy of a third booster dose of the vaccine will be evaluated in Phase 2 and 3 clinical trials.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.