Phase 1 /2 data from Oxford COVID-19 vaccine – immunogenic and well-tolerated

July 21, 20200

The Oxford University – AstraZeneca non-replicating viral vector vaccine for COVID-19 is one of the 6 candidates globally that have now advanced to Phase III clinical validation.  Oxford University has now announced the first set of results from phase 1/ 2 trial of its COVID vaccine ChAdOx1. The results published in Lancet showed promising data indicating that the vaccine is safe and immunogenic. The trial was conducted at five sites in UK with 1077 trial participants in two groups which included 543 to receive ChAdOx1 and 534 to receive MenACWY (Meningococcal vaccine) as the control. A dose of 5 × 10¹⁰ viral particles was chosen based on the dose-response relationship observed in the previously developed MERS vaccine on the same platform. 10 participants from the investigational group also received a second prime-boost dose 28 days after the first dose. Co-primary endpoints of the study were to study vaccine efficacy, measured by the number of symptomatic COVID-19 cases and safety, measured by the occurrence of any adverse events.  

Preliminary results from the trial indicated that the vaccine was well-tolerated with mild reactogenicity that was alleviated by prophylactic use of paracetamol and there were no other severe adverse events observed. The vaccine induced both cellular and humoral immune response in the recipients  spike specific T-cell responses peaked on day 14 and anti-spike IgG response peaked at day 28 and were boosted following a second dose in the 10 participants. Neutralizing antibody responses against live SARS-CoV-2 were measured using different assays in a smaller group of 35 participants which received a single dose. 32 out of these 35 participants (91%) achieved neutralizing antibody titers when measured using micro-neutralization assay (MNA80) and in 100% patients when measured using plaque reduction neutralization test (PRNT50). Following a booster dose, 100% participants (10/10) showed neutralizing titers at day 42 as measured by MNA80and at day 56 measured by Marburg virus neutralization assay. While booster dose showed significantly elevated levels of neutralizing antibodies, future studies will be needed to study any anti-vector antibodies produced on homologous boosting that may cause some unwanted immune response as the current data has a clear evidence of a boosted immune response after the second shot.  

 The correlation of neutralizing titers with the IgG levels identified through ELISA indicates that a standardised ELISA may be sufficient to predict protection in larger populations if the neutralizing antibodies demonstrate long-term protection in vaccinated individuals. This would require establishing standard antibody and assay standards to bridge the immunogenicity and serology data across different vaccine candidates and expedite the development of other vaccine candidates.  

Establishing means to facilitate bridging studies across vaccines candidates has become vital today as multiple developers rush to push their vaccines through clinical development and licensure. The results from the first-in-human trial are promising and offer hope that a vaccine may soon be availableA final Phase 3 trials initiated in larger and more diverse population sets in Brazil, South Africa, and UK will offer greater confidence in the safety and efficacy of the vaccine.  While the clinical trials indicate promising results, its collaborator AstraZeneca has been partnering with a number of organizations to produce more than 2 billion doses of the much-awaited vaccine and has made supply commitments across the globe.  Global partnerships such as with Serum Institute in India are also catalytic in accelerating clinical development and global market access in addition to creating much needed scale of manufacturing in a globally distributed manner.  

 

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