There's hope. Results of two early phase COVID-19 vaccine trials have been published in The Lancet, and both have reported “encouraging” results. The two vaccines are from the UK and China—Jenner Institute at Oxford University, UK, that is developing the candidate with support from pharma company AstraZeneca, and CanSino Biologics in Wuhan, China.
In vaccine development, early trials (phase one and two) are done to test safety and immune responses generated, while phase 3 trials indicate efficacy of the vaccine as they are tested on a large population. The vaccines have been found to be safe, and have generated good immune response, results published in the medical journal suggest.
“Both groups used an adenoviral vector, and both report the vaccine achieving humoral responses (immune response that involves antibodies secreted by B cells and circulating in bodily fluids) to the SARS-CoV-2 spike glycoprotein receptor binding domain by day 28 as well as T-cell responses. Both report local and systemic mild adverse events such as fever, fatigue, and injection site pain. In neither trial was a severe adverse event reported,” according to The Lancet commentary on the latest results published on July 20.
Adenovirus vector vaccines are the latest in vaccine development and employ an engineered version of an adenovirus that acts as a vector for a gene from the surface protein of SARS-CoV2.
According to the Lancet, the Oxford group tested (phase 1/2 randomised trial) the chimpanzee adenovirus-vectored COVID-19 vaccine against a comparator quadrivalent conjugate meningococcal vaccine among 1,077 healthy adults (50 per cent male) between 18–55 years, recruited from five centres in the UK and followed up for 28 days. A subset of the subjects (10 people) received two doses of the vaccine. The vaccine provoked a T cell response within 14 days of vaccination (white blood cells that can attack cells infected with the SARS-CoV-2 virus), and an antibody response within 28 days (antibodies are able to neutralise the virus so that it cannot infect cells when initially contracted).
During the study, participants who received the vaccine had detectable neutralising antibodies, which have been suggested by researchers as important for protection, and these responses were the strongest after a booster dose, with 100 per cent of participants' blood having neutralising activity against the coronavirus. The next step in studying the vaccine is to confirm that it can effectively protect against SARS-CoV-2 infection.
“The Phase I/II data for our coronavirus vaccine shows that the vaccine did not lead to any unexpected reactions and had a similar safety profile to previous vaccines of this type. The immune responses observed following vaccination are in line with what previous animal studies have shown are associated with protection against the SARS-CoV-2 virus, although we must continue with our rigorous clinical trial programme to confirm this in humans,” Professor Andrew Pollard, chief investigator of the Oxford Vaccine Trial at Oxford University and co-author of the study, said in a statement.
“We saw the strongest immune response in the 10 participants who received two doses of the vaccine, indicating that this might be a good strategy for vaccination,” Professor Pollard said. The study also reported adverse events such as fatigue, headache, and local tenderness, but found these to be tolerable and mostly ameliorated by paracetamol. "No serious adverse events occurred,” the results read. “These encouraging results support further evaluation of this candidate vaccine in our ongoing large scale Phase III programme, that is still needed to assess the ability of the vaccine to protect people from COVID-19,” Sarah Gilbert, Professor of Vaccinology, at the University of Oxford Jenner Institute and co-author of the study, said in the statement.
Neutralising antibodies—all antibodies generated in the body against an infection are not protective, and researchers need to look for neutralising antibodies—were generated in more than 90 per cent of participants. The antibody responses were sustained up to 56 days of observation. Besides, researchers report T cell responses were also induced in all participants. “In this vaccine trial, scientists are looking for both B cells for antibodies and cytotoxic T cells from the T-cell basket. Both these have their own function. The cytotoxic T cells will perform the function of killing the infected cells in the body, while the antibodies will be binding with the surface antigen of virus and neutralize the virus,” said Dr. Sunit K. Singh, professor and head, molecular biology, Institute of Medical Sciences, Banaras Hindu University.
“The vaccine developed by Oxford University has shown some positive signs of protection in the preliminary results of the early trial. It is being claimed that it will be more effective than others because it will develop antibodies and "natural killer cells" (T-cells) against SARS-COV2. But the biggest challenge would be the longevity of the (neutralising) antibodies,” Singh told THE WEEK.
In SARS-CoV-2, antibodies are known to fade between three-six months, as reported by various studies, he said. “So what would be the fate of protection induced by a vaccine once the antibody response vanishes or is reduced? A virus of this kind will certainly need an attack from both sides—the antibodies and T cells,” he added.
The Chinese vaccine results from the phase 2 randomised trial also reported no serious adverse events, and T cell responses.
The Lancet comment on the trial results also prescribes caution, and says that phase 3 trials—where the vaccines would be tested on much larger populations of participants to assess their efficacy and safety—would be crucial.
“Much remains unknown about these and other COVID-19 vaccines in development, including longevity of response and immunogenicity in older adults or other specific groups, such as those with comorbidities who are often excluded from clinical trials, or ethnic or racial groups more severely affected by COVID-19,” the commentary reads.
While the safety signals from these two important trials are “reassuring”, experts suggest comprehensive and transparent evaluation of risks and honest communication of potential harms.