Two candidate vaccines (ChAdOx1 and Ad-5-nCoV) for Covid-19 have been shown to be safe and efficacious in humans, according to two studies published this week in The Lancet journal.
Both vaccines are based on adenovirus vectors, DNA viruses that act as vehicles to carry SARS-CoV-2 proteins to the body, therefore eliciting a response against an infection.
ChAdOx1
Developed by the Jenner Institute, at Oxford, and by the biopharmaceutical AstraZeneca, ChAdOx1 elicited an immune response in all participants, recruited in five locations in the UK, of combined phases 1 and 2 of the trials.
A single dose (5×1010 viral particles per ml) of the vaccine induced a strong T-cell response against SARS-CoV-2 14 days after vaccination and prevailed for, at least, two months. These findings corroborate the initial evidence that T-cell may play an important role in fighting SARS viruses, even when the infection does not elicit the production of antibodies.
The ChAdOx1 vaccine also proved to be efficacious in eliciting an antibody response. Antibodies levels against SARS-CoV-2 spike protein rose after vaccination, peaked one month later, and remained elevated two months later. The ten participants who received a booster dose registered even higher antibodies levels. Additionally, the Oxford team showed that, in three independent assays, antibodies were actively neutralising the virus.
Fatigue, headaches, and chills were the most common self-reported adverse reactions to the vaccine, even though the prophylactic use of paracetamol increased its tolerability. Most participants registered mild-to-moderate symptoms, and no participant reported serious adverse effects.
Ad-5-vectored vaccine
The first phase of the Ad-5 vaccine trials started in March 2020, in Wuhan, China. Now, after moving to a larger scale of testing, the results of Phase 2 have been published in The Lancet. The full data of Phase 1 is yet to be analysed.
While the Oxford group used a single vaccine concentration, researchers from the Beijing Institute for Biotechnology and CanSino Biologics tested two different doses (1×1011 and 5×1010 viral particles per ml). A single injection of Ad-5 vaccine induced a significant immune response in the two groups, including neutralising antibodies against live SARS-CoV-2 and T-cell responses in most participants, compared to the group who received the placebo.
Pre-existing immunity against the viral vector, adenovirus type-5 have been found to be the biggest obstacle against the development of this vaccine. In particular, older people tend to have a history of exposure to adenovirus type-5 and may need a higher dose or a booster to develop an adequate immune response to this candidate vaccine.
[su_note note_color=”#fdf13d” text_color=”#0d0d0c”]One critical difference between these viral vectors may determine how effective these vaccines are: while the ChAdOx1 vaccine is engineered from a virus that causes infections in chimpanzees, and thus it is very unlikely that humans have a pre-existing immune response against it, the Ad-5-nCov vaccine is based on adenovirus-type-5, a virus that infects people; therefore, it is possible that an immune response triggered by the vaccine may happen because the body recognizes the viral vector and not the SARS-CoV-2 protein sequence. [/su_note]
For Phase 3, a double-blind (neither participants nor researchers know who is taking the vaccine or the placebo), randomised trial, with one single dose (5×1010 viral particles) will test effectiveness in large-scale. Meanwhile, the Chinese military personal has already received approval to be vaccinated.
Sources:
Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., Yau, Y. (2020). Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet. doi:10.1016/s0140-6736(20)31604-4
Zhu, F., Guan, X., Li, Y., Huang, J., Jiang, T., Hou, L., Chen, W. (2020). Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: A randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. doi:10.1016/s0140-6736(20)31605-6
