Nav: Home

The Lancet Infectious Diseases: Preliminary results find vaccine candidate based on inactivated SARS-CoV-2 virus is safe and induces an immune response in healthy volunteers

October 15, 2020

Peer reviewed / Randomised clinical trial / People

The Lancet Infectious Diseases: Preliminary results find vaccine candidate based on inactivated SARS-CoV-2 virus is safe and induces an immune response in healthy volunteers
  • Phase 1/2 randomised controlled trial of an inactivated SARS-CoV-2 vaccine candidate was carried out in China between 29 April and 30 July 2020 and involved more than 600 healthy volunteers.
  • Study detected antibody responses in all recipients by day 42 after vaccination, and provides some data for participants aged over 60 years.
  • The vaccine was safe and well tolerated at all tested doses, with no severe adverse reactions reported. The most common reported side effect was pain at the injection site.
  • The primary objective was to evaluate the immune response and safety of the vaccine, and the study was not designed to assess how effective it is at preventing infection with SARS-CoV-2.
A Chinese COVID-19 vaccine candidate based on the inactivated whole SARS-CoV-2 virus (BBIBP-CorV) is safe and elicits an antibody response, findings from a small early-phase randomised clinical trial published today in The Lancet Infectious Diseases journal have found.

A previous clinical trial reported similar results for a different vaccine that is also based on inactivated whole SARS-CoV-2 virus, but in that study the vaccine was only tested in people aged under 60 years.

The latest study included participants aged between 18 and 80 years, and found that antibody responses were induced in all recipients. Participants aged 60 and over were slower to respond, taking 42 days before antibodies were detected in all recipients compared with 28 days for participants aged 18-59. Antibody levels were also lower in those aged 60-80 years compared with those aged 18-59 (Mean neutralising antibody titre 42 days after receiving a 8μg vaccine dose was 228.7 for people aged 18-59, and 170.9 for those aged 60-80) [1].

The trial was not designed to assess efficacy of the vaccine, so it is not possible to say whether the antibody responses induced by the vaccine, called BBIBP-CorV, are sufficient to protect from SARS-CoV-2 infection.

Professor Xiaoming Yang, one of the authors of the study, from the Beijing Institute of Biological Products Company Limited, Beijing, China, said: "Protecting older people is a key aim of a successful COVID-19 vaccine as this age group is at greater risk of severe illness from the disease. However, vaccines are sometimes less effective in this group because the immune system weakens with age. It is therefore encouraging to see that BBIBP-CorV induces antibody responses in people aged 60 and older, and we believe this justifies further investigation." [2]

There are currently 42 vaccines for COVID-19 in clinical trials [3]. These vary in type and include DNA plasmid vaccines, inactivated virus vaccines, adenovirus-vectored vaccines, RNA vaccines, protein subunit vaccines and virus-like particle vaccines. Some of these have already been shown to be safe and to elicit immune responses in early phase clinical trials.

The BBIBP-CorV vaccine used in the study reported here is based on a sample of the virus that was isolated from a patient in China. Stocks of the virus were grown in the lab using cell lines and then inactivated using a chemical called beta-proprionolactone. BBIBP-CorV includes the killed virus mixed with another component, aluminium hydroxide, which is called an adjuvant because it is known to boost immune responses.

The first phase of the study was designed to find the optimal safe dose for BBIBP-CorV. It involved 96 healthy volunteers aged between 18 and 59 years and a second group of 96 participants aged between 60 years and 80 years. Within each group, the vaccine was tested at three different dose levels (2?g, 4?g and 8?g, 24 participants per group), with two vaccinations administered on day 0 and 28. A fourth group within each age group (24 participants in each age group) were given two doses of a placebo vaccine. In total, in phase 1 of the study, 144 participants received the vaccine and 48 received the placebo.

The second phase of the study was designed to identify the optimal timing schedule for vaccination. 448 participants aged between 18 and 59 years were randomly assigned to receive either one 8?g shot of vaccine or placebo, or two shots of 4?g vaccine or placebo (at 0 and 14 days, 0 and 21 days or 0 and 28 days). In this second phase, there were 112 participants per group, with 336 receiving the vaccine, and 112 receiving the placebo.

Participants were asked to report any adverse events for the first seven days after each vaccination and these were verified by the research team. Thereafter, participants recorded any adverse events using paper cards for the following 4 weeks. During phase 1, laboratory tests were carried out after the first and second vaccinations to assess kidney function, liver function and other organ functions. Blood samples were taken to test antibody levels for SARS-CoV-2 before and after vaccination.

No serious adverse events were reported within 28 days of the final vaccination. The most common side effect was pain at the injection site (phase 1 results: 24% [34/144] of vaccine recipients, vs 6% [3/48] of placebo recipients). A small number of participants reported experiencing a fever (phase 1 results: 4% [5/144] of vaccine recipients, vs 6% [3/48] of placebo recipients). There were no instances of clinically significant changes in organ functions detected in laboratory tests in any of the groups.

The greatest antibody responses were elicited by two 4?g doses of the vaccine at either days 0 and 21 or 0 and 28 (Mean neutralising antibody titres 28 days after second vaccination were 282.7 for two 4?g injections at day 0 and 21, and 218.0 for two 4?g injections at day 0 and 28).

Professor Xiaoming Yang said: "Our findings indicate that a booster shot is necessary to achieve the greatest antibody responses against SARS-CoV-2 and could be important for protection. This provides useful information for a phase 3 trial." [2]

The authors noted some limitations with the study, including the short duration of follow up at just 42 days. They also highlighted that the study did not include children and adolescents aged under 18. Trials with these groups will be carried out when the full analysis of data from adult groups is completed, the researchers say.

Writing in a linked Comment article, Professor Larisa Rudenko, who was not involved in the study, from the Institute of Experimental Medicine, Saint Petersburg, Russia, said: "[...] more studies are needed to establish whether the inactivated SARS-CoV-2 vaccines are capable of inducing and maintaining virus-specific T-cell responses, because CD4-positive T-cell help is important for optimal antibody responses, as well as for cytotoxic CD8-positive T-cell activation, which, in turn, are crucial for viral clearance if neutralising antibody-mediated protection is incomplete."
-end-
NOTES TO EDITORS

This study was carried out by researchers from the Henan Provincial Center for Disease Control and Prevention (China), The Beijing Institute of Biological Products (China), the Chinese Center for Disease Control and Prevention (China), The National Institute for Food and Drug Control (China), Tsinghua University (China), and Beijing Zhongsheng Hengyi Pharmaceutical Technology (China). It was funded by the National Program on Key Research Project of China, National Mega Projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation and the Beijing Science and Technology Plan.

The labels have been added to this press release as part of a project run by the Academy of Medical Sciences seeking to improve the communication of evidence. For more information, please see: http://www.sciencemediacentre.org/wp-content/uploads/2018/01/AMS-press-release-labelling-system-GUIDANCE.pdf

if you have any questions or feedback, please contact The Lancet press office pressoffice@lancet.com

[1] Mean neutralising antibody titre measures the average of reciprocal of the highest dilution protecting 50% of cells from virus challenge.

[2] Quote direct from author and cannot be found in the text of the Article.

[3] WHO draft landscape of COVID-19 candidate vaccines
https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (Accessed 6 October 2020).

The Lancet

Related Immune Response Articles:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.
Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.
Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.
Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.
Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.
Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.
'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.
A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.
Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.
How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.
More Immune Response News and Immune Response Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Sound And Silence
Sound surrounds us, from cacophony even to silence. But depending on how we hear, the world can be a different auditory experience for each of us. This hour, TED speakers explore the science of sound. Guests on the show include NPR All Things Considered host Mary Louise Kelly, neuroscientist Jim Hudspeth, writer Rebecca Knill, and sound designer Dallas Taylor.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

Kittens Kick The Giggly Blue Robot All Summer
With the recent passing of Ruth Bader Ginsburg, there's been a lot of debate about how much power the Supreme Court should really have. We think of the Supreme Court justices as all-powerful beings, issuing momentous rulings from on high. But they haven't always been so, you know, supreme. On this episode, we go all the way back to the case that, in a lot of ways, started it all.  Support Radiolab by becoming a member today at Radiolab.org/donate.