Mixed schedules involving the Pfizer/BioNTech and Oxford/AstraZeneca vaccines generate strong immune response against the SARS-CoV2 spike IgG protein, according to findings from the Com-COV study led by the University of Oxford.
In a paper published on the Lancet pre-print server, researchers report that both mixed schedules (Pfizer/BioNTech followed by Oxford/AstraZeneca, and Oxford/AstraZeneca followed by Pfizer/BioNTech) induced high concentrations of antibodies against the SARS-CoV2 spike IgG protein when doses were administered 4 weeks apart.
The trial recruited 830 volunteers aged 50 and above from eight National Institute for Health Research (NIHR) supported sites in England to evaluate the four different combinations of prime and booster vaccination.
In April, the researchers expanded the programme to include the Moderna and Novavax vaccines in a new study, run across nine NIHR supported sites and backed through funding from the Vaccines Taskforce and the Coalition for Epidemic Preparedness Innovations.
The six new ‘arms’ of the trial each recruited approximately 175 candidates, adding a further 1070 recruits into this programme.
The latest results show that the order of vaccines makes a difference, with the Oxford/AstraZeneca followed by Pfizer-BioNTech schedule inducing higher antibodies and T-cell responses than Pfizer-BioNTech followed by Oxford/AstraZeneca.
Both schedules inducing higher antibodies than the licensed, and highly effective standard two-dose Oxford/AstraZeneca schedule. The highest antibody response was seen after the two-dose Pfizer/BioNTech schedule, and the highest T cell response with Oxford/AstraZeneca followed by Pfizer/BioNTech.
'Vital Step Forward'
Professor Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and chief investigator on the trial, said: “The results show that when given at a 4-week interval, both mixed schedules induce an immune response that is above the threshold set by the standard schedule of the Oxford/AstraZeneca vaccine.
“These results are an invaluable guide to the use of mixed dose schedules, however the interval of four weeks studied here is shorter than the eight to 12-week schedule most commonly used for the Oxford-AstraZeneca vaccine. This longer interval is known to result in a better immune response, and the results for a 12-week interval will be available shortly.
England's Deputy Chief Medical Officer Professor Jonathan Van-Tam said the data are a vital step forward, however, he said, given the UK’s stable supply position there is no reason to change vaccine schedules at this moment in time.
“Our non-mixed (homologous) vaccination programme has already saved tens of thousands of lives across the UK but we now know mixing doses could provide us with even greater flexibility for a booster programme, while also supporting countries who have further to go with their vaccine rollouts and who may be experiencing supply difficulties,” he said.
In May, researchers reported preliminary Com-COV data revealing more frequent mild to moderate reactions in mixed schedules compared to standard schedules, however, these were short-lived in duration.
'Beautifully Designed Study'
Other experts have commented via the Science Media Centre.
Peter Openshaw, professor of experimental medicine, Imperial College London, said: "This beautifully designed study has already reported on the side effects of the ‘mix and match’ approach, and now reports the immunology results of the one-month dose interval. The most interesting aspect is that the antibody responses were best with the two-dose Pfizer/BioNTech schedule, whereas the best T cell responses were in those who had the AstraZeneca followed by Pfizer vaccines. Which of these is more protective in the long run remains to be determined, but in the meantime the study is reassuring that using a mixed vaccine approach is not only safe but can potentially give immune responses that are as good or better than those induced by single vaccine regimens. Being able to boost with a different vaccine would add flexibility to the vaccine programme. The next set of data from the 12 week dose interval is keenly awaited."
Prof Paul Hunter, professor in medicine, UEA, said: "This latest paper is an important contribution to the debate about whether it is better to give identical vaccines for first or second boost (homologous prime boost) or to give vaccines from different manufacturers for the second dose (heterologous prime boost). Given that we have already given second doses to over 60% of the adult population in the UK, the findings of this study are unlikely to affect strategy for the first and second doses but this could have major impact on strategy for a booster campaign in the autumn."
Dr Peter English, retired consultant in communicable disease control, said: "This paper’s findings...are no surprise to vaccinologists. They confirm what we had predicted. But it remains very important to check that our predictions were correct, and this paper does just that."
Liu X, Shaw RH, Stuart ASV, Greenland M, Dinesh T, Provstgaard-Morys S. Safety and immunogenicity report from the Com-COV study – A single-blind randomised non inferiority trial comparing heterologous and homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine. Lancet pre-print. Published 28 June 2021.
This article was adapted from Univadis, part of the Medscape Professional Network.
