An Immunobridging Study to Evaluate the Neutralizing Antibody Titer in Adults Immunized with Two Doses of Either ChAdOx1-nCov-19 (AstraZeneca) or MVC-COV1901

Abstract

Rapid development and deployment of vaccines is crucial to control the continuously evolving COVID-19 pandemic. The placebo-controlled phase 3 efficacy trial is still the standard for authorizing vaccines in the majority of the world. However, due to a lack of eligible participants in parts of the world, this has not always been feasible. Recently, the Taiwan Food and Drug Administration, following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. Here, we describe a study in which our candidate vaccine, MVC-COV1901, an adjuvanted protein subunit vaccine, has been granted emergency use authorization (EUA) in Taiwan based on a noninferiority immunobridging study. Immunogenicity results from the per protocol immunogenicity (PPI) subset (n = 903) from the MVC-COV1901 phase 2 trial were compared with results from 200 subjects who had received an adenovirus vector vaccine, AstraZeneca ChAdOx nCOV-19 (AZD1222), in a separate study. The lower bound of the 95% confidence interval (CI) of the geometric mean titer (GMT) ratio comparing MVC-COV1901 to AZD1222 was 3.4. The lower bound of the 95% CI of the sero-response rate was 95.5%. Both the GMT ratio and sero-response rate exceeded the criteria established by the Taiwan regulatory authority, leading to EUA approval of MVC-COV1901 in Taiwan.

A randomized controlled trial of heterologous ChAdOx1 nCoV-19 and recombinant subunit vaccine MVC-COV1901 against COVID-19

“…The primary objective of this trial was to determine if the immune response (neutralizing antibody titer at day 28 after the booster dose) of heterologous group was non-inferior to that observed in the homologous group (Supplementary Note 1 ). The non-inferiority study design was based on the immuno-bridging standards in granting Emergency Use Authorization for COVID-19 vaccine (including MVC-COV1901) by Taiwan FDA ( https://www.fda.gov.tw ) 20 . The immuno-bridging success criteria was the lower limit of the 2-sided 95% confidence interval (CI) for geometric mean titer (GMT) ratio >0.67 20 .…”

“…The non-inferiority study design was based on the immuno-bridging standards in granting Emergency Use Authorization for COVID-19 vaccine (including MVC-COV1901) by Taiwan FDA ( https://www.fda.gov.tw ) 20 . The immuno-bridging success criteria was the lower limit of the 2-sided 95% confidence interval (CI) for geometric mean titer (GMT) ratio >0.67 20 .…”

An Evaluation of the Safety and Immunogenicity of MVC-COV1901: Results of an interim analysis of a phase III, parallel group, randomized, double-blind, active-controlled study

“…Levels of binding and neutralizing antibodies can be correlated and used to predict vaccine efficacy [23,24]. Reported antibody titers induced by two doses of MVC-COV1901concur with those found in previous studies [8,12] which is estimated to confer 90% vaccine efficacy against the ancestral strain [8,9]. The emergence of the other strains and particularly the Omicron strain, however, has increased ability of the virus to evade immunity, rendering two doses of currently available vaccines, largely ineffective in neutralization [25-27].…”

“…An immunobridging assessment demonstrated non-inferiority in terms of immunogenicity to AZD1222 with a geometric mean titer (GMT) of neutralizing antibodies equivalent to 3.8 times that of AZD1222. [9]. In terms of safety, the V-Watch program, launched by the Taiwan Centers for Disease Control to monitor post-marketing safety, reported no serious adverse effects for MVC in 2 million doses administered [10].…”

Boosting with Multiple Doses of mRNA Vaccine after Priming with Two Doses of Protein Subunit Vaccine MVC-COV1901 Elicited Robust Humoral and Cellular Immune Responses against Emerging SARS-CoV-2 Variants

“…Since AZ was the first COVID-19 vaccine to be approved in Taiwan, it was chosen as the comparator vaccine with locally developed MVC ( 12 ). We first measured the RNA-binding domain (RBD)-specific IgG titers of individuals with different vaccination schedules against different SARS-CoV-2 variants using enzyme-linked immunosorbent assay (ELISA) ( Fig.…”