- Phase 2 Randomized Controlled Trial of a Recombinant Adenovirus Type 5 Vector COVID-19 The vaccine (Ad5 vectorized COVID-19 vaccine) was carried out in China in April 2020 and involved more than 500 people.
- The main objective of the study was to assess the immune response and safety of the vaccine, and determine the most appropriate dose for a phase 3 trial.
- Phase 3 trials are needed to confirm whether the vaccine candidate effectively protects against SARS-CoV-2 infection
According to new research published in a phase 2 trial of an Ad5 vectorized COVID-19 vaccine candidate, conducted in China, the vaccine is safe and induces an immune response. The lancet.
The randomized trial sought to assess the safety and immunogenicity of the vaccine candidate and follows a phase 1 trial published in May 2020. The results provide data from a larger group of participants than their phase 1 trial, including a small subset of participants. aged 55 years and older, and will report phase 3 trials of the vaccine.
However, the authors note that it is important to note that no participant was exposed to the SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine whether the vaccine candidate effectively protects against infection by SARS-CoV-2.
Professor Feng-Cai Zhu, Provincial Center for Disease Control and Prevention, Jiangsu, China, says: “The phase 2 trial adds more evidence on safety and immunogenicity in a large population than the phase 1 trial. This is one step important in evaluating this early-stage experimental vaccine and phase 3 trials are now underway. ” [2]
Currently, there are around 250 candidate SARS-CoV-2 vaccines in development worldwide, including mRNA vaccines, viral replicating or non-replicating viral vaccines, DNA vaccines, autologous dendritic cell vaccines and inactive virus vaccines. At least 17 of them are currently under evaluation in clinical trials.
The vaccine in this trial uses a weakened human common cold virus (adenovirus, which infects human cells easily but is unable to cause disease) to deliver genetic material encoding the SARS-CoV-2 tip protein to cells. These cells then produce the spike protein and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight the coronavirus.
508 participants participated in the trial of the new vaccine. Of these, 253 received a high dose of the vaccine (at 1 × 1011 viral particles / 1.0 ml), 129 received a low dose (at 5 × 1010 viral particles / 1.0 ml) and 126 received placebo. Approximately two thirds of the participants (309; 61%) were between 18 and 44 years old, a quarter (134; 26%) were between 45 and 54 years old, and 13% (65) were 55 years old or older.
Participants were monitored for immediate adverse reactions for 30 minutes after injection and followed up for any adverse site or systemic adverse reactions within 14 and 28 days after vaccination. Serious adverse events reported by participants throughout the study period were documented. Blood samples were taken from participants immediately before vaccination and 14 and 28 days after vaccination to measure antibody responses.
The trial found that 95% (241/253) of participants in the high-dose group and 91% (118/129) of recipients in the low-dose group showed daily T cell or antibody immune responses. 28 after vaccination.
The vaccine induced a neutralizing antibody response in 59% (148/253) and 47% (61/129) of the participants, and the binding antibody response in 96% (244/253) and 97% (125/129) of the participants, in the high and low dose groups, respectively, on day 28. Participants in the placebo group showed no increase in antibodies from baseline.
Both doses of the vaccine induced significant neutralizing antibody responses to live SARS-CoV-2, with geometric mean titers of 19.5 and 18.3 in the participants who received the high and low doses, respectively. The binding antibody response peaked at 656.5 ELISA units and 571 ELISA units for the high and low dose of the vaccine, respectively.
T-cell responses were also found in 90% (227/253) and 88% (113/129) of the participants who received the vaccine in high and low doses, respectively. A median of 11 spot-forming cells and 10 spot-forming cells per 1 × 10? Peripheral blood mononuclear cells were observed in participants in the high-dose and low-dose groups, respectively, on day 28.
The proportions of participants who had an adverse reaction such as fever, fatigue and pain at the injection site were significantly higher in vaccine recipients than in placebo recipients (72% [183/253] in the high-dose group, 74% [96/129] in the low dose group, 37% [46/126] in the placebo group). However, most adverse reactions were mild or moderate. At 28 days, 24 (9%) participants in the high-dose group had serious adverse reactions (grade 3), which were significantly higher than in those who received the low-dose or placebo (one participant (1%) in the group low dose, and 2 people (2%) in the placebo group). The most common severe reaction was fever.
The authors note that pre-existing immunity to the human adenovirus that was used as the vector (i.e., the Ad5 vector) for this vaccine and increasing age could partially hinder vaccination-specific immune responses, particularly for antibody responses. . Among the 508 participants, 266 (52%) participants showed high pre-existing immunity to the Ad5 vector, while 242 (48%) had low pre-existing immunity to the Ad5 vector. Those with higher pre-existing anti-Ad5 immunity showed a lower immune response (levels of neutralizing and binding antibodies were approximately twice as high in people with low pre-existing anti-Ad5 immunity, compared to those with high pre-existing immunity). Compared to the younger population, older participants generally had significantly lower immune responses and greater tolerability to the Ad5 vectorized COVID-19 vaccine.
Professor Wei Chen of the Beijing Institute of Biotechnology, China says: “Since older people face a high risk of serious illness and even death associated with COVID-19 infection, they are an important target population for a vaccine COVID-19. An additional dose may be needed to induce a stronger immune response in the elderly population, but more research is being done to assess this. “
The authors note that the trial was conducted in Wuhan, China, and the reference immunity is representative of Chinese adults at the time, but other countries may have different immunity rates that should be considered. Furthermore, the trial only followed participants for 28 days and this study has no data on the durability of vaccine-induced immunity. Importantly, no participant was exposed to the SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine the efficacy of the candidate vaccine or any immune risk associated with the vaccine-induced antibody when you are exposed to the virus.
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Reference: “Immunogenicity and safety of a recombinant adenovirus type 5 vectorized COVID-19 vaccine in healthy adults 18 years of age and older: a randomized, double-blind, placebo-controlled, phase 2 trial” by Feng-Cai Zhu, Xu -Hua Guan, Yu-Hua Li, Jian-Ying Huang, Tao Jiang, Li-Hua Hou, Jing-Xin Li, Bei-Fang Yang, Ling Wang, Wen-Juan Wang, Shi-Po Wu, Zhao Wang, Xiao- Hong Wu , Jun-Jie Xu, Zhe Zhang, Si-Yue Jia, Bu-Sen Wang, Yi Hu, Jing-Jing Liu, Jun Zhang, Xiao-Ai Qian, Qiong Li, Hong-Xing Pan, Hu-Dachuan Jiang, Peng Deng , Jin-Bo Gou, Xue-Wen Wang, Xing-Huan Wang, and Wei Che, July 20, 2020, The lancet.
DOI: 10.1016 / S0140-6736 (20) 31605-6
This study was funded by China’s National Key R&D Program, National Science and Technology Major Project, and CanSino Biologics. It was conducted by researchers from the Jiangsu Provincial Center for Disease Control and Prevention, Hubei Provincial Center for Disease Control and Prevention, National Institute for Food and Drug Control, Zhongnan Hospital of Wuhan University, Institute of Microbiology and Epidemiology of Beijing, State Pathogen Laboratory. and Biosecurity, Beijing Institute of Biotechnology, Academy of Military Medical Sciences, CanSino Biologics, Shanghai Canming Medical Technology. The authors’ declaration of interests is provided in the document.
