Results of the Phase-2 trial of the Oxford vaccine show that the vaccine is safe across age groups — younger (18-55 years age) and older adults (over 56 years age). In fact, older adults better tolerated the vaccine than younger adults, the results show. The vaccine also induced T cell immune responses and neutralising antibodies in all adults across age groups.
Results of Phase-2 trail of the Oxford vaccine (ChAdOx1 nCoV-19) show that the vaccine is safe across age groups — younger (18-55 years age) and older adults (over 56 years age). In fact, older adults better tolerated the vaccine than younger adults, the results show. The vaccine also induced good immune responses — T cell immune responses and neutralising antibodies — in all adults across age groups.
The results were published online in The Lancet on November 19. The results are based on the study of 560 participants enrolled between May 30 and August 8. Of the 560, 160 participants were aged 18-55 years (100 got the vaccine and the remaining 60 belonged to the active control arm). Those in the active control arm received a vaccine (MenACWY) which gives protection against four types of meningococcal disease. The analysis included another 160 participants aged 56-69 years (120 got the vaccine and 40 got the active control vaccine), 240 participants were over 70 years of age (200 got the vaccine and 40 got the MenACWY vaccine).
The COVID-19 vaccine candidate was administered as a single-dose or two-dose regimen 28 days apart as either a low or a standard dose.
The most common adverse effect seen in those who received the COVID-19 vaccine were injection-site pain, fever, muscle ache, and headache. These adverse events were less common in older adults (aged over 56 years) than younger adults. Thirteen serious adverse events occurred in the six months since the first dose was given, none of which were related to the COVID-19 vaccine or MenACWY vaccine.
Fewer adverse events were reported after the boost vaccination than after the first or prime vaccination.
The vaccine was found to induce both T cell responses and neutralising antibodies in all age groups. The vaccine induced a T cell response peaked 14 days of the first dose of vaccination (across all age groups and vaccine dose), while neutralising antibody response was observed within 28 days of the booster dose of vaccination. The T cell immune response (also called cellular immune response) finds and kills cell infected with the virus, while neutralising antibody response (also called humoral immune response) finds and attacks the virus circulating in the blood or lymphatic system.
There is increasing evidence that T-cells play an important role in preventing serious disease with natural infection of the COVID-19 virus, while neutralising antibodies help prevent infection.
The ChAdOx1 nCoV-19 vaccine induced antibodies against the virus 28 days after the first dose of the vaccine across all age groups. Following the booster dose of the vaccine, antibody levels increased at day 56 of the trial, irrespective of dose or age of the participants. Importantly, neutralising antibodies too were seen at day 42, two weeks after the booster vaccine dose. Two weeks after the booster dose, more than 99% (208 of 209) of participants of who received the COVID-19 vaccine across all age groups had neutralising antibody responses.
“Neutralising antibodies are thought to be associated with protection, and in a COVID-19 non-human primate challenge model, neutralising antibody responses correlated with protection,” the authors write.
“The robust humoral and cellular immune responses obtained in our older adult population were encouraging given that a number of studies have shown that decreasing immune function with age leads to decreased immune responses to vaccines,” the authors write.
Significance of Phase-2 trial
“Our findings show that the ChAdOx1 nCoV-19 vaccine was safe and well tolerated with a lower reactogenicity profile in older adults than in younger adults. Immunogenicity was similar across age groups after a boost vaccination,” they write. “If these responses correlate with protection in humans, these findings are encouraging because older individuals are at disproportionate risk of severe COVID-19 and so any vaccine adopted for use against SARS-CoV-2 must be effective in older adults.”
Neutralising antibodies in younger and older adults in a dose-dependent manner in the case of Pfizer and Moderna vaccine. While the immunogenicity decreased with age in the case of the Pfizer vaccine, neutralising antibody responses appeared to be similar in adults older than 56 years and those aged 18-55 years in the case of Moderna vaccine.
It was though that Oxford vaccine that used adenovirus-vector platform might not produce good immune responses due to pre-existing as the antibody response to adenovirus. It was to circumvent this that the Oxford vaccine used a chimpanzee adenovirus. Though adenovirus-vector platform against SARS-CoV-2 have shown reduced immune responses in older age group, the COVID-19 vaccine has been able to elicit the same immune response level in both younger and older age groups.
The Pune-based Serum Institute will be manufacturing the vaccine for distribution in India and other developing countries. Serum Institute will be manufacturing 200 million doses of the vaccine for low- and middle-income countries as part of the Gavi COVAX Advance Market Commitment.
Serum Institute has completed phase-2 trial in India and has already completed enrollment of participants for the Phase-3 trial of the vaccine Covishield.