COVID-19 vaccine candidates induce immune reaction

Wednesday, 22 July, 2020

COVID-19 vaccine candidates induce immune reaction

The Lancet has published early results from two promising new SARS-CoV-2/COVID-19 vaccine candidates, one being trialled in the UK and the other in China.

UK trial

A phase 1/2 trial of the UK vaccine, designed by scientists from the University of Oxford’s Jenner Institute and Oxford Vaccine Group, indicated no early safety concerns and showed that the vaccine induces strong immune responses in both parts of the immune system. The randomised study of over 1000 participants showed that the vaccine provoked a T cell response within 14 days of vaccination and an antibody response within 28 days, which is in line with previous SARS-Cov-2 studies in animals.

“The new vaccine is a chimpanzee adenovirus viral vector (ChAdOx1) vaccine that expresses the SARS-CoV-2 spike protein,” explained lead author Professor Andrew Pollard from the University of Oxford. “It uses a common cold virus (adenovirus) that infects chimpanzees, which has been weakened so that it can’t cause any disease in humans, and is genetically modified to code for the spike protein of the human SARS-CoV-2 virus. This means that when the adenovirus enters vaccinated people’s cells it also delivers the spike protein genetic code. This causes these people’s cells to produce the spike protein, and helps teach the immune system to recognise the SARS-CoV-2 virus.

“The immune system has two ways of finding and attacking pathogens — antibody and T cell responses. This vaccine is intended to induce both, so it can attack the virus when it’s circulating in the body, as well as attacking infected cells. We hope this means the immune system will remember the virus, so that our vaccine will protect people for an extended period.”

The authors found that there were strong antibody and T cell responses from the vaccine. T cell responses targeting the SARS-CoV-2 spike protein were markedly increased in the 43 participants studied, peaking 14 days after vaccination, with this level declining slightly by day 56 of the trial. The T cell response did not increase with a second dose of the vaccine, which is consistent with other vaccines of this kind.

Antibody responses meanwhile peaked by day 28 and remained high until the measurement at day 56 in the trial for those given a single vaccine; this response was boosted by a second dose. 28 days after vaccination, neutralising antibody responses against SARS-CoV-2 were detected in 32 of 35 participants (when measured in MNA80 neutralisation assay) and in 35 of 35 participants (when measured in PRNT50 neutralisation assay) who received a single dose of the COVID-19 vaccine. These responses were present in all participants who had a booster dose of the vaccine.

The vaccine was found to have an acceptable safety profile, similar to previous vaccines of this type, and there were no unexpected or serious adverse reactions, even though it was given in a high dose. Fatigue and headache were the most commonly reported reactions, with other common side effects including pain at the injection site, muscle ache, malaise, chills, feeling feverish and high temperature.

Participants taking paracetamol around their vaccination had reduced pain, chills, feeling feverish, muscle ache, headache and malaise in the two days following vaccination. In addition, in the 10 people who received the extra dose of the COVID-19 vaccine, side effects were less common after the second dose. The authors found that taking paracetamol did not affect immunogenicity of the COVID-19 vaccine.

The authors note some limitations, including that more research is needed to confirm their findings in different groups of people — including older age groups, those with other health conditions, and in ethnically and geographically diverse populations; these groups are being recruited in their ongoing phase 2 and 3 trials of the vaccine in the UK, Brazil and South Africa. They also note that a small number of participants had detectable neutralising antibodies and T cell responses against SARS-CoV-2 spike protein before vaccination, likely to be due to past asymptomatic infection as potential participants with a history of COVID-19 (either diagnosed or suspected) were excluded from the study.

The participants recruited in this study will be followed up for at least one year to continue to study the vaccine’s safety and the immune response it provokes. The scientists will meanwhile continue their study of the vaccine to confirm that it can effectively protect against SARS-CoV-2 infection, while also collaborating with AstraZeneca on plans for further development, large-scale manufacture and potential distribution.

“There is still much work to be done before we can confirm if our vaccine will help manage the COVID-19 pandemic, but these early results hold promise,” said study co-author Professor Sarah Gilbert from the University of Oxford. “As well as continuing to test our vaccine in phase 3 trials, we need to learn more about the virus — for example, we still do not know how strong an immune response we need to provoke to effectively protect against SARS-CoV-2 infection. If our vaccine is effective, it is a promising option as these types of vaccine can be manufactured at large scale.”

Chinese trial

Meanwhile, a phase 2 trial of an Ad5 vectored COVID-19 vaccine candidate — conducted by CanSino Biologics and China’s military research unit — has found that the vaccine is safe and induces an immune response.

The randomised trial of over 500 participants sought to evaluate the safety and immunogenicity of the vaccine candidate and follows a phase 1 trial published in May. The results provide data from a wider group of participants than their phase 1 trial, including a small subgroup of participants aged over 55 years and older, and will inform phase 3 trials of the vaccine.

As in the Oxford trial, the vaccine in this trial uses a weakened adenovirus to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognise that spike protein and fight off the coronavirus.

The trial found that 95% of participants in the high-dose group and 91% of the recipients in the low-dose group showed either T cell or antibody immune responses at day 28 post-vaccination. A neutralising antibody response was induced in 59% and 47% of participants in the high- and low-dose groups respectively, and binding antibody response in 96% and 97% of participants, by day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2. T cell responses were also found in 90% and 88% of participants receiving the vaccine at high and low dose respectively.

The proportions of participants who had adverse reactions such as fever, fatigue and injection-site pain were significantly higher in vaccine recipients than those in placebo recipients; however, most adverse reactions were mild or moderate. Within 28 days, 9% of participants in the high-dose group had severe adverse reactions, compared to 1% of participants in the low-dose group, and 2% of the placebo group. The most common severe reaction was fever.

The authors note that no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine whether the vaccine candidate effectively protects against SARS-CoV-2 infection. They also noted that pre-existing immunity to the human adenovirus which was used as the vector (ie, the Ad5 vector) for this vaccine and increasing age could partially hamper the specific immune responses to vaccination, particularly for the antibody responses. Those with a higher pre-existing anti-Ad5 immunity showed an inferior immune response; this was the case particularly in older participants, who had higher tolerability to the Ad5 vectored COVID-19 vaccine.

“Since elderly individuals face a high risk of serious illness and even death associated with COVID-19 infection, they are an important target population for a COVID-19 vaccine,” said study co-author Professor Wei Chen, from the Beijing Institute of Biotechnology. “It is possible that an additional dose may be needed in order to induce a stronger immune response in the elderly population, but further research is underway to evaluate this.”

Co-author Professor Feng-Cai Zhu, from the Jiangsu Provincial Center for Disease Control and Prevention, concluded, “The phase 2 trial adds further evidence on safety and immunogenicity in a large population than the phase 1 trial. This is an important step in evaluating this early-stage experimental vaccine and phase 3 trials are now underway.”

Image credit: © CHETRONI

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