A Phase III Randomized Controlled Trial Assessing the Safety and Immunogenicity of Biological E’s XBB 1.5 RBD Subunit COVID-19 Booster Vaccine in Individuals Aged 5 to 80 Years
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
The SARS-CoV-2 virus continues to evolve with recent iterations such as the Omicron sub-variants having potential for increased transmissibility. Of particular interest, the XBB.1.5 variant has been shown to cause vaccine-breakthrough cases. Biological E (BE) has utilized the same platform it used to develop CORBEVAX TM , an ancestral Wuhan strain COVID-19 RBD subunit vaccine (control vaccine), to now develop an XBB.1.5 RBD subunit vaccine (test vaccine).
Methods
To assess the safety and immunogenicity of BE’s new XBB.1.5 subunit vaccine, a prospective, randomized, single-blind Phase III study was conducted in participants aged 5 to 80 years. Participants who had not received any other approved COVID-19 vaccine within the last 6 months prior were enrolled and randomized 2:1 to receive two booster doses of either the test vaccine or the control vaccine. The vaccines were administered on Day 0 and Day 28 with immunogenicity assessments on Day 0, Day 28, and Day 42. Safety assessments included the collection of solicited and unsolicited adverse events (AEs) up until Day 56. The primary objective of the study was to show immunogenic superiority of the test vaccine booster series compared to the control vaccine series. This superiority objective was to be concluded if the lower limit of the two-sided 95% confidence interval of the anti-XBB.1.5.RBD neutralizing antibody (nAb) geometric mean titer (GMT) ratio of test:control was >1.0 on either Day 28 or Day 42. Given the emergence of JN.1 as the SARS-CoV-2 strain during the conduct of this study, Day 42 anti-JN.1 nAb were measured in a post hoc immunogenicity assessment. In addition, anti-XBB.1.5 RBD protein IgG concentration in the sera samples were also measured by ELISA on Day 0, Day 28, and Day 42.
Findings
A total of 360 participants were enrolled and randomized across 7 sites in India. The nAb GMT ratio of test:control participants was 2.08 (95% CI 1.64 to 2.63) on Day 28 and 2.91 (95% CI 2.38 to 3.56) on Day 42. The geometric mean fold rise (GMFR) of neutralizing antibodies (nAb) was 7.637 (95% CI 6.090 to 9.578) on Day 28 and 17.02 (95% CI 13.79 to 21.01) on Day 42 in the test booster series arm. The nAb GMFRs in the control booster series arm at the same time points were 3.033 (95% CI 2.340 to 3.932) and 4.824 (95% CI 3.731 to 6.236) respectively. Post hoc analyses revealed an nAb GMT ratio of 1.90 (95% CI 1.56 to 2.31) of test:control against the JN.1 SARS-CoV-2 strain. The safety profile of the new XBB.1.5 RBD subunit vaccine was found to be very similar to that of the Ancestral strain vaccine with 59 AEs (about 1 AE for every 8 doses administered) and 27 AEs (a little less than 1 AE for every 8 doses administered) respectively during the study. No serious AEs or AEs of special interest were reported in either the test or control arm of the study. Two cases of pyrexia were medically attended to, one in each arm.
Interpretations
Biological E’s new XBB.1.5 RBD subunit vaccine was found to be both safe and robustly immunogenic when administered as a two-dose booster series in 5 to 80 year olds. In particular, the vaccine induced a significant rise in neutralizing antibodies against the XBB.1.5 strain as well as cross-protective neutralizing antibodies against the JN.1 SARS-CoV-2 strain. These data are in line with studies of other XBB.1.5 monovalent vaccines and support a positive risk-benefit profile. Real world studies may provide additional evidence about the effectiveness of this new updated vaccine.
CTRI Trial Registration Identifier
CTRI/2024/01/061423
Funding
Biological E Limited.
Research in context
Evidence before this study
The SARS-CoV-2 virus has been circulating worldwide ever since its emergence in late 2019. Vaccinations have been particularly useful in preventing hospitalizations and deaths even in those that acquire COVID-19. Multiple technology platforms have been utilized to develop vaccines including mRNA and protein subunit platforms. More recently, immune-evasive SARS-CoV-2 strains have emerged fueling the need for variant-directed boosters. Multiple mRNA monovalent boosters and one protein subunit booster targeting the XBB.1.5 strain have been approved by different national regulatory agencies across the world.
Added value of this study
In this study, we tested a new XBB.1.5 RBD subunit vaccine that was developed using an established yeast-expression system. We ran a single-blinded randomized Phase III study to compare two booster doses of this updated vaccine versus two booster doses of the ancestral strain vaccine developed on the same yeast-expression system. We showed that the safety profile of the two vaccines was comparable. The older of these vaccines has now been safely administered to over 40,000,000 people and has been shown to have an acceptable safety profile. Additionally, the XBB.1.5 RBD subunit vaccine was found to be superior to the ancestral strain vaccine in inducing neutralizing antibodies against the XBB.1.5 strain. Importantly, this updated vaccine also induced neutralizing antibodies against the JN.1 strain, which became the most prevalent circulating SARS-CoV-2 strain during and after the conduct of the study. This study demonstrates a favourable risk-benefit profile of the updated monovalent XBB.1.5 RBD subunit vaccine when administered as a booster series across multiple age groups including children as young as 5 years.
Implications of all the available evidence
Our study adds to the growing body of evidence suggesting the use of updated monovalent booster vaccines will be useful in curtailing the morbidity and mortality of the SARS-CoV-2 virus. Various real-world studies have demonstrated the effectiveness of such updated vaccines in preventing hospitalizations and deaths. Protein subunit vaccines such as ours have been extensively used over the past many decades and are more likely to be accepted in an environment of growing vaccine-hesitancy. SARS-CoV-2 vaccines developed on newer platforms such as the mRNA platform and the adenoviral vector platform, while faster to market, have been shown to induce rare but serious adverse events such as myocarditis and thrombosis. Protein subunit SARS-CoV-2 vaccines do not seem to produce as many adverse events suggesting a superior safety profile.
