Comparable safety and non-inferior immunogenicity of the SARS-CoV-2 mRNA vaccine candidate PTX-COVID19-B and BNT162b2 in a phase 2 randomized, observer-blinded study

Abstract

In the aftermath of the COVID-19 pandemic, the evolution of the SARS-CoV-2 into a seasonal pathogen along with the emergence of new variants, underscores the need for dynamic and adaptable responses, emphasizing the importance of sustained vaccination strategies. This observer-blind, double-dummy, randomized immunobridging phase 2 study (NCT05175742) aimed to compare the immunogenicity induced by two doses of 40 μg PTX-COVID19-B vaccine candidate administered 28 days apart, with the response induced by two doses of 30 µg Pfizer-BioNTech COVID-19 vaccine (BNT162b2), administered 21 days apart, in Nucleocapsid-protein seronegative adults 18-64 years of age. Both vaccines were administrated via intramuscular injection in the deltoid muscle. Two weeks after the second dose, the neutralizing antibody (NAb) geometric mean titer ratio and seroconversion rate met the non-inferiority criteria, successfully achieving the primary immunogenicity endpoints of the study. PTX-COVID19-B demonstrated similar safety and tolerability profile to BNT162b2 vaccine. The lowest NAb response was observed in subjects with low-to-undetectable NAb at baseline or no reported breakthrough infection. Conversely, participants who experienced breakthrough infections during the study exhibited higher NAb titers. This study also shows induction of cell-mediated immune (CMI) responses by PTX-COVID19-B. In conclusion, the vaccine candidate PTX-COVID19-B demonstrated favourable safety profile along with immunogenicity similar to the active comparator BNT162b2 vaccine.

Figure 1

Study profile and participant disposition. Enrollment and follow-up of study participants vaccinated with 40 μg PTX-COVID19-B or 30 µg BNT162b2 after the first and second dose administration. EIP evaluable immunogenicity population, mITT modified Intent-to-Treat population, n number of participants.

Figure 2

Solicited systemic and local adverse events (AEs) 7 days after each dose. The systemic (A) and local (B) AEs are reported by dose, treatment and maximum severity. Participants were monitored for solicited systemic and local AEs from the time of vaccination through 7 days after each dose. Occurrence of the events from Grade 1 to Grade 3 are represented as percentage of participants. No Grade 4 (potentially life-threatening) events were reported by participants.

Figure 3

Humoral response. Neutralizing antibody (NAb) titers were measured by ancestral strain derived vesicular stomatitis virus pseudovirus neutralization assay in (A) the Evaluable Immunogenicity Population (EIP), (B) the EIP with NAb titers ≤ 30 NT50 at baseline and C) the modified Intent-to-Treat population (mITT). (D) Anti-Spike IgG were measured by ELISA in the mITT population. Geometric mean titers (GMT) including values at the top of the corresponding histograms ± 95% Confidence Interval (CI) represented. The covariance analysis (SAS) of comparing GMT at Day 35/42 in the EIP participants (primary immunological endpoint) are summarized at the top of the corresponding time point histograms (A, B). † Indicates statistically significant (p ≤ 0.0001, paired t-test on log-transformed values, SAS) differences from all other treatment-matched time points. The p values for all the other comparisons are presented within group across timepoints (C, D).

Figure 4

Cell-mediated immunity. IFN-γ response was measured in the modified Intent-to-Treat population by ELISpot. Mean of Spot Forming Cell (SFC) counts per 10⁶ cells ± 95% Confidence Interval (CI) are represented. † Indicates statistically significant (p ≤ 0.0001) differences from all other treatment-matched time. The p values for all the other comparisons are presented as within group values at each timepoint or between group values across timepoints (paired t-test on log-transformed values, SAS).

Figure 5

Mucosal immunity. Anti-Spike and anti-Receptor Binding Domain (RBD) IgG, IgA and associated secretory component were measured by ELISA at serial dilutions in 17 participants (mITT). The Area Under the Curve (AUC) was then normalized and expressed as % of internal positive control consisting of saliva collected from COVID-19 acute and convalescent patients.

Figure 6

Time to COVID-19 infection. Cumulative incidence of COVID-19 infection free participants in seronegative modified Intent-to-Treat population starting 2 weeks after the first vaccine dose. COVID-19 cases were confirmed by PCR-positive nasopharyngeal swabs and/or reactive serum antibody test results.