In the hunt for a vaccine against Covid-19, encouraging news emerged about two candidates on Wednesday. The New England Journal of Medicine published an interim analysis describing an immune response generated in participants of phase I clinical trials for a candidate vaccine, developed by US-based biotech company Moderna. Meanwhile, ITV reported that there could be positive news, possibly by Thursday, on initial trials of another candidate vaccine, from the University of Oxford.
What are these two candidates?
Moderna was the first company to begin a human trial for a candidate vaccine against Covid-19. Called mRNA-1273, the vaccine went into phase I trials on March 16. The vaccine uses mRNA technology, which involves injecting genetic instructions to human cells for creating proteins to fight the virus. The details of the phase I trial come two weeks before Moderna begins phase III on July 27.
Oxford University has developed its candidate vaccine, ChAdOx1 nCoV-19, in partnership with global biopharmaceutical firm AstraZeneca. It delivers a SARS-CoV-2 protein to induce an immune response. The vaccine has already gone into phase III trials, but the results of phase I are yet to be announced.
During human clinical trials, three aspects are assessed: reactogenicity (ability to produce common, adverse reactions), immunogenicity (ability to provoke an immune response), and safety.
What are the results of the phase I trials on Moderna’s candidate vaccine?
The interim analysis found there was a vaccine-induced immune response in all the participants. During phase I, 15 participants received a low dose of 25 micrograms, 15 received a medium dose of 100 micrograms, and 15 received a high dose of 250 micrograms. Two shots were given, one month apart.
The study found that greater reactogenicity followed the second vaccination, particularly in the 250-microgram group. Also, of the three doses evaluated, the 100-microgram dose elicited high neutralisation responses and T cell responses, “coupled with a reactogenicity profile that is more favorable than that of the higher dose”. In phase III, the participants will be administered the 100-microgram dose.
Were there side effects?
The study reported fatigue, chills, headache, myalgia, and pain at the injection site, reported in more than half the participants. It said the two-dose vaccine series “was generally without serious toxicity”. Systemic adverse events after the first vaccination, when reported, were “all graded mild or moderate”.
“After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-microgram group, 10 (67%) in the 100- microgram group, and 8 (53%) in the 250- microgram group; all were mild or moderate in severity,” the study said. Adverse events were more common after the second vaccination, “and occurred in 7 of 13 participants (54%) in the 25-microgram group, all 15 in the 100-microgram group, and all 14 in the 250-microgram group, with 3 of those participants (21%) reporting one or more severe events.”
What is the news about the University of Oxford’s vaccine candidate?
“I am hearing there will be positive news soon (perhaps tomorrow) on initial trials of the Oxford Covid-19 vaccine that is backed by AstraZeneca and supported by tens of millions of pounds of government money,” ITV’s political editor Robert Peston wrote. “The first data is due be published in the Lancet.”
For phase I in April, 1,102 participants were recruited in multiple study sites in the UK. On May 22, Oxford announced that 1,000 immunisations “have been completed and follow-up is currently ongoing”. Professor Andrew Pollard, head of the Oxford Vaccine Group, said in a statement: “The clinical studies are progressing very well and we are now initiating studies to evaluate how well the vaccine induces immune responses in older adults, and to test whether it can provide protection in the wider population.”
On June 27, Brazil began a phase III trial of the Oxford candidate, with 5,000 healthy volunteers targeted for enrolment. Trials will be conducted in South Africa too.
How significant are the findings of phase I of a trial?
Phase I of a clinical trial only provides evidence of a vaccine’s safety and its ability to generate an immune response. As such, it gives an indication of what is the ideal dose required to administer in the next stage.
The critical question that remains unanswered in this phase is: how long do the antibodies last to provide immunity against the virus?. Also, phase I involves a small number of participants. In phase II, the age range of participants is expanded to see if there is variation in the immune response between older people and children. Phase III, which involves a very large group, investigates how well the vaccine works to prevent a larger community from being infected.
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What is the status of other vaccine candidates that have entered phase III?
Pfizer and its French partner BioEnTech, which uses the same mRNA technology as the Moderna candidate, announced an interim report of early-stage trials on July 1. The study, which has not been peer-reviewed, found neutralising antibodies on day 21 of vaccination.
Another major player is the Chinese biopharmaceutical company Sinovac Biotech, which has partnered with Brazil’s Butantan to develop CoronaVac, an inactivated vaccine candidate. The company announced earlier this month that CoronaVac was granted approval for the phase III trial by the Brazilian National Regulatory Agency. The trial will recruit 9,000 healthcare professionals from Covid-19 health facilities in 12 sites in Brazil. Enrolment is expected to start this month after ethical approval is obtained from the 12 selected sites.
Brazil’s approval came on the basis of preliminary results of phases I and II conducted in Jiangsu province beginning April 16, and announced on June 13. The company said there has been no severe adverse event reported in either the phase I, which had 143 healthy volunteers, or phase II trials, which had 600 healthy volunteers. “The phase II clinical trial results show that the vaccine induces neutralising antibodies 14 days after the vaccination…,” the company said.
The company said it will be submitting the phase II study report and phase III clinical study protocol to the Chinese regulator in the “near future”. “The Company expects to share the full data on our clinical trials with the public through academic publications,” it said.
This article first appeared in the print edition on July 16, 2020 under the title ‘Twin hopes on vaccine front’.
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