Preliminary findings from a Phase I/II trial published Monday in The Lancet showed that AZD1222, the COVID-19 vaccine AstraZeneca is co-developing with the University of Oxford, increased levels of both neutralising antibodies and T-cells that target the SARS-CoV-2 virus. The Oxford researchers said results from the COV001 study, which began in April, signalled no early safety concerns, while "a single dose elicited both humoral and cellular responses against SARS-CoV-2, with a booster immunisation augmenting neutralising antibody titers."
The news follows the publication of an interim analysis in the NEJM last week showing that a two-dose vaccination schedule of Moderna's experimental coronavirus vaccine mRNA-1273 induced anti–SARS-CoV-2 immune responses in all 45 study participants, including "robust" neutralising antibody titers, as well as Th1-biased CD4 T-cell responses (for related analysis, see ViewPoints: After Phase I data, it’s a good day to be Moderna). Meanwhile, Pfizer and partner BioNTech have recently reported promising data for their BNT162 programme from Phase I/II studies conducted in the US and Germany, with the mRNA-based vaccine BNT162b1 eliciting high SARS-CoV-2 neutralising titers and strong CD4+ and CD8+ T-cell responses.
Andrew Pollard, chief investigator of the Oxford trial, stated that the interim Phase I/II data for AZD1222, which also goes by the name ChAdOx1 nCoV-19, show it "did not lead to any unexpected reactions and had a similar safety profile to previous vaccines of this type." Meanwhile, the immune responses "are in line with what we expect will be associated with protection against the SARS-CoV-2 virus," with the strongest response seen in the 10 participants who received two doses, "indicating that this might be a good strategy for vaccination," he said.
In the trial, between April 23 and May 21, 1077 healthy volunteers aged between 18 and 55 years were randomised to receive AZD1222 or placebo MenACWY vaccine. Further, 10 participants assigned to a non-randomised, unblinded prime-boost group received a two-dose schedule of AZD1222, with the booster vaccine administered 28 days after the first.
According to AstraZeneca, results showed that a single dose of AZD1222 led to a four-fold increase in antibodies to the SARS-CoV-2 virus spike protein in 95% of participants one month after injection. Meanwhile, the experimental vaccine induced a T-cell response in all participants, which peaked by day 14 and was maintained two months after injection. Findings also indicated that AZD1222 induced neutralising antibodies against SARS-CoV-2, which were detected in 91% of 35 participants using one test, or 100% of 35 participants using another test, following a single dose. After the booster injection, researchers said all participants had neutralising activity. "Neutralising antibody responses correlated strongly with antibody levels measured by ELISA," the authors noted, adding that "although a correlate of protection has not been defined for COVID-19, high levels of neutralising antibodies have been shown in convalescent individuals, with a wide range, as confirmed in our study."
Meanwhile, local and systemic reactions were more common in the AZD1222 group in the trial, including pain, feeling feverish, chills, muscle ache, headache and malaise, although the study authors said these were alleviated by use of prophylactic paracetamol, and there were no serious adverse events related to the vaccine.
Adrian Hill, head of Oxford's Jenner Institute, highlighted the fact that AZD1222 elicited neutralising antibodies after a single dose, which may be an important advantage in quickly raising immunity. "I don't read that clearly in the Moderna data…I think they need two doses to see plausibly protective neutralising antibodies," Hill remarked, adding that AstraZeneca will prioritise a booster regimen in future testing. Moderna is set to begin Phase III testing of mRNA-1273 on July 27.
Mene Pangalos, who heads BioPharmaceuticals R&D at AstraZeneca, remarked that "while there is more work to be done, today's data increases our confidence that the vaccine will work and allows us to continue our plans to manufacture the vaccine at scale for broad and equitable access around the world." Phase II/III trials of the vaccine are currently under way in the UK, Brazil and South Africa, and are due to start in the US.
Commenting on the news, Mizuho Securities analyst Vamil Divan said "importantly, today's data includes the first evidence of the vaccine generating a T-cell response, which could be critical in order for patients to develop durable immunity to the novel coronavirus." Nevertheless, AstraZeneca investors appeared less than pleased with the data readout, with company shares dipping 3.2% in afternoon trading, a reaction Bernstein's Ronny Gal suggested was due to the fact that while AZD1222 induced neutralising antibody titers in all study subjects, they were lower than the sera of patients who have recovered from coronavirus infections.
Meanwhile, SVB Leerink analysts highlighted the uncertainty surrounding immunity with such a novel virus. "What remains unknown is whether the antibody response translates into protection, the level of neutralising antibodies required for durable protection, and the role of T-cell immunity in the process," they said. For more analysis, see ViewPoints: The COVID-19 vaccine race gets competitive – but should it?
Separately on Monday, The Lancet also published Phase II results for CanSino Biologic's recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine candidate, dubbed Ad5-nCoV, demonstrating that it was safe and induced immune responses in most of the recipients after a single immunisation. The trial, conducted in Wuhan, China, included 508 healthy participants aged 18 years or older who were randomised to receive the vaccine at one of two doses, or placebo.
Results showed that in the low and high viral particle dose groups, the receptor binding domain-specific ELISA antibodies peaked at 656.5 and 571, with seroconversion rates at 96% and 97%, respectively, at day 28. In addition, the authors said both doses of the vaccine induced "significant" neutralising antibody responses to live SARS-CoV-2, with geometric mean titres of 19.5 and 18.3, respectively. Meanwhile, solicited adverse reactions were reported by 72% of 253 and 74% of 129 participants in the two groups, respectively, although no serious adverse reactions were documented.
In May, Phase I trial data, also published in The Lancet, showed that the vaccine was tolerable and immunogenic at 28 days post-vaccination. Meanwhile, last month, China's military cleared use of CanSino's vaccine for a period of one year.
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