Thuluva Subhash, Paradkar Vikram, Gunneri SubbaReddy, Mogulla Rammohan Reddy, Yerroju Vijay, Dhar Chirag, Ningaiah Siddalingaiah, Panchakshari Mallikarjuna, Gillurkar Chandrashekhar S, Narang Manish, Kisan Shivnitwar Sachin, Rao A Venkateshwar
Biological E Limited, Hyderabad, Telangana, India.
Gillurkar Multispeciality Hospital, Nagpur, Maharashtra, India.
Lancet Reg Health Southeast Asia. 2025 Jul 24;40:100642. doi: 10.1016/j.lansea.2025.100642. eCollection 2025 Sep.
The SARS-CoV-2 virus continues to evolve with recent variants such as the omicron sub-variants potentially exhibiting increased transmissibility. Of note, the XBB.1.5 variant has been associated with vaccine-breakthrough cases. We utilised the same platform previously used to develop CORBEVAX™, an ancestral Wuhan strain COVID-19 RBD subunit vaccine, to now develop an XBB.1.5 RBD subunit vaccine. We evaluated the safety and immunogenicity of the new XBB.1.5 RBD subunit vaccine compared to an ancestral Wuhan strain RBD subunit vaccine.
This prospective, single-blind, phase 3 randomised controlled trial was conducted in participants aged 5-80 years. Participants who had not received any other approved COVID-19 vaccine within the last 6 months were enrolled and randomised in a 2:1 ratio 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 to Day 56. The primary objective of the study was to demonstrate immunogenic superiority of the test vaccine booster series compared to the control vaccine series. This superiority objective was to be met if the lower limit of the two-sided 95% CI of the anti-XBB.1.5.RBD neutralising antibody (nAb) geometric mean titre (GMT) ratio of test: control was >1.0 on either Day 28 or Day 42. Given the emergence of JN.1 as the prevalent SARS-CoV-2 strain during the conduct of this study, Day 42 anti-JN.1 nAb levels were measured in a immunogenicity assessment. In addition, anti-XBB.1.5 RBD protein IgG concentrations were also measured by ELISA on Day 0, Day 28, and Day 42. The trial was registered at Clinical Trials Registry-India as CTRI/2024/01/061423.
A total of 360 participants (32.8% female) were enrolled and randomised across seven sites in India. The nAb GMT ratio of test: control participants was 2.08 (95% CI 1.64-2.63) on Day 28 and 2.91 (95% CI 2.38-3.56) on Day 42. The geometric mean fold rise (GMFR) of neutralising antibodies (nAb) was 7.637 (95% CI 6.090-9.578) on Day 28 and 17.02 (95% CI 13.79-21.01) 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 2.340-3.932) and 4.824 (95% CI 3.731-6.236), respectively. analyses revealed an nAb GMT ratio of 1.90 (95% CI 1.56-2.31) for 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 required medical attention, one in each arm.
The 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 individuals aged 5-80 years. In particular, the vaccine induced a significant rise in neutralising antibodies against the XBB.1.5 strain as well as cross-protective neutralising 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.
Biological E Limited, India.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒持续演变，近期的变异株如奥密克戎亚变体可能具有更高的传播性。值得注意的是，XBB.1.5变异株与疫苗突破病例有关。我们利用先前用于研发CORBEVAX™（一种源自武汉毒株的新冠病毒受体结合域（RBD）亚单位疫苗）的相同平台，来研发一种XBB.1.5 RBD亚单位疫苗。我们将新的XBB.1.5 RBD亚单位疫苗与源自武汉毒株的RBD亚单位疫苗进行比较，评估了其安全性和免疫原性。
这项前瞻性、单盲、3期随机对照试验在5至80岁的参与者中进行。招募过去6个月内未接种过任何其他获批新冠疫苗的参与者，并按2:1的比例随机分组，分别接受两剂试验疫苗或对照疫苗的加强针。疫苗在第0天和第28天接种，并在第0天、第28天和第42天进行免疫原性评估。安全性评估包括收集直至第56天的主动和被动不良事件（AE）。该研究的主要目的是证明试验疫苗加强针系列相对于对照疫苗系列在免疫原性上具有优越性。如果试验组与对照组抗XBB.1.5.RBD中和抗体（nAb）几何平均滴度（GMT）比值的双侧95%置信区间下限在第28天或第42天大于1.0，则达到这一优越性目标。鉴于在本研究进行期间JN.1成为流行的SARS-CoV-2毒株，在一项免疫原性评估中测量了第42天的抗JN.1 nAb水平。此外，还在第0天、第28天和第42天通过酶联免疫吸附测定（ELISA）测量抗XBB.1.5 RBD蛋白IgG浓度。该试验在印度临床试验注册中心注册，注册号为CTRI/2024/01/061423。
共有360名参与者（32.8%为女性）入组并在印度的7个地点进行随机分组。试验组与对照组参与者的nAb GMT比值在第28天为2.08（95%置信区间1.64 - 2.63），在第42天为2.91（95%置信区间2.38 - 3.56）。试验加强针系列组中，中和抗体（nAb）的几何平均倍增率（GMFR）在第28天为7.637（95%置信区间6.090 - 9.578），在第42天为17.02（95%置信区间13.79 - 21.01）。对照组加强针系列组在相同时间点的nAb GMFR分别为3.033（95%置信区间2.340 - 3.932）和4.824（95%置信区间3.731 - 6.236）。分析显示，试验组与对照组针对JN.1 SARS-CoV-2毒株的nAb GMT比值为1.90（95%置信区间1.56 - 2.31）。发现新的XBB.1.5 RBD亚单位疫苗的安全性与源自原始毒株的疫苗非常相似，研究期间分别有59例不良事件（每接种约8剂出现1例不良事件）和27例不良事件（每接种约8剂出现略少于1例不良事件）。研究的试验组或对照组均未报告严重不良事件或特别关注的不良事件。有2例发热需要医疗处理，每组各1例。
在5至80岁个体中作为两剂加强针系列接种时，新的XBB.1.5 RBD亚单位疫苗被发现既安全又具有强大的免疫原性。特别是，该疫苗诱导了针对XBB.1.5毒株的中和抗体显著升高，以及针对JN.1 SARS-CoV-2毒株的交叉保护性中和抗体。这些数据与其他XBB.1.5单价疫苗的研究结果一致，并支持其良好的风险效益比。真实世界研究可能会提供有关这种新的更新疫苗有效性的更多证据。
印度生物E有限公司。
