Oxford-AstraZeneca COVID-19 Vaccine Displays Immune Response

July 21, 2020 - A recent clinical trial found that a new COVID-19 vaccine candidate, ChAdOx1 nCoV-19, given as a single dose was safe and well tolerated, according to a new study published in Lancet. 

For more coronavirus updates, visit our resource page, updated twice daily by Xtelligent Healthcare Media.

Specifically, the study showed that the COVID-19 vaccine created by Oxford University and AstraZeneca prompted neutralizing antibody responses against SARS-CoV-2. It wasdetected in 91 percent of participants after a single dose when measured in microneutralization assay and in 100 percent of participants when measured plaque reduction neutralization assay.

Humoral responses to SARS-CoV-2 spike protein peaked by day 28-post prime, and cellular responses were induced in all participants by day 14. After two doses, notable cellular and humoral immunogenicity was present in all participants. 

These results support large-scale evaluation of this candidate vaccine in an ongoing phase 3 program, according to the study. 

“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 Andrew J. Pollard, BSc MBBS PhD (Lond), DIC, MRCP (UK), FHEA, FIDSA, FRCPCH, MA, FMedSci, a member of the Oxford Vaccine Group, said in a statement.

The Phase 1/2, single-blind, randomized controlled trial enrolled 1077 healthy adults aged 18-55 years with no history of COVID-19 between April 23 and May 21, 2020, in the UK.

The participants received ChAdOx1 nCoV-19 at a dose of 5×10 viral particles or MenACWY as a single injection. 

Although there were minor reactions reported, local and systemic reactions were more common in the ChAdOx1 nCoV-19 group. These reactions included pain, fevers, chills, muscle ache, headache, and malaise.

These symptoms were quickly reduced when paracetamol was used prophylactically for the first 24 hours after vaccination. 

There were no serious adverse events related to ChAdOx1 nCoV-19 reported. 

“In conclusion, ChAdOx1 nCoV-19 was safe, tolerated, and immunogenic, while reactogenicity was reduced with paracetamol. A single dose elicited both humoral and cellular responses against SARS-CoV-2, with a booster immunization augmenting neutralizing antibody titers,” researchers said in the study.

“The preliminary results of this first-in-human clinical trial supported clinical development progression into ongoing phase 2 and 3 trials.”

Researchers noted that they identified one published clinical trial in China of an adenovirus-5-vectored vaccine against SARS-CoV-2, using a single dose at three different dose levels.

The Phase 2, randomized, double blind, placebo-controlled trial, enrolled 508 volunteers between April 11 and 16, 2020 in Wuhan, China. Individuals received the vaccine or placebo. 

A single injection of the Ad5-vectored COVID-19 vaccine at 1×10 viral particles and 5×10 viral particles induced comparable specific immune responses to the spike glycoprotein at day 28, with no significant differences noted between the two groups.

And both doses of the vaccine induced significant neutralizing antibody responses, with geometric mean titers (GMTs) of 19.5 and 18.3 in participants receiving 1×10 and 5×10 viral particles, respectively, researchers said.

But the Ad5-vectored COVID-19 vaccine at 5×10 viral particles was safe and induced a more notable immune response in the majority of recipients after a single immunization.

In those two groups, the RBD-specific ELISA antibodies peaked at 656·5 as well. 

“Our results suggest a single-dose immunization schedule of Ad5-vectored COVID-19 vaccine at 5 × 10 viral particles is an appropriate regimen for healthy adults. Compared with the younger population, we found older people to have a significantly lower immune response, but higher tolerability, to the Ad5-vectored COVID-19 vaccine,” researchers explained in the study.

“Therefore, an additional dose might be needed to induce a better immune response in the older population, and this will be evaluated in a phase 2b trial.”

Both the Oxford University trial and the Wuhan, China trial were shown to be promising for the future of the COVID-19 pandemic and met similar endpoints. 

There were local and systemic mild adverse events reported in both trials, including fever, fatigue, and injection site pain. But neither trial reported a serious adverse event.

“These trial reports are hugely anticipated. The results of both studies augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety,” experts at Johns Hopkins University said in a separate commentary. 

“Both trials used adenovirus vectors to deliver and study the COVID-19 vaccine, an innovative and efficient means of vaccine development in the midst of apandemic. Capable of generating humoral, cellular, and innate responses, adenovirus-vectored vaccines have much potential.”