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Mixing COVID-19 vaccinations gives better immune response — Oxford trial

People had a better immune response when they received a first dose of AstraZeneca or Pfizer-BioNTech shots followed by Moderna nine weeks late, found an Oxford University study in The Lancet.

“We found a really good immune response across the board…, in fact, higher than the threshold set by Oxford-AstraZeneca vaccine’s two doses,” Matthew Snape, the Oxford professor behind the trial dubbed Com-COV2, told Reuters.

“The data from this study will be especially interesting and valuable to countries where they're still rolling out the first two doses of vaccines,” Snape said.“We’re showing…you don’t have to stick rigidly to receiving the same vaccine for a second dose…and that if the programme will be delivered more quickly by using multiple vaccines, then it is okay to do so.”

If the AstraZeneca-Oxford vaccine is followed by a Moderna or Novavax shot, higher antibodies and T-cell responses were induced versus two doses of AstraZeneca-Oxford.

The study of 1,070 volunteers also found that a dose of the Pfizer- BioNTech (PFE.N), (22UAy.DE) vaccine followed by a Moderna (MRNA.O) shot was better than two doses of the standard Pfizer-BioNTech course.

Pfizer-BioNTech followed by Novavax induced higher antibodies than the two-dose Oxford-AstraZeneca schedule, although this schedule induced lower antibody and T-cell responses than the two-dose Pfizer-BioNTech schedule.

No safety concerns were raised.

Many countries have been deploying a mix and match well before robust data were available as nations were faced with soaring infection numbers, low supplies and slow immunisation over some safety concerns. Longevity of protection offered by vaccines has been under scrutiny, with booster doses being considered as well amid surging cases. New variants, including Delta and Omicron, have now increased the pressure to speed up vaccination campaigns, adds Reuters.

Blood samples from participants were tested against the Wild-Type, Beta
and Delta variants, researchers of the Com-COV2 study said, adding that vaccines’ efficacy against the variants had waned, but this was consistent across mixed courses.

Deploying vaccines using technology from different platforms, like Pfizer and Moderna’s mRNA, AstraZeneca's viral vector and Novavax’s protein-based shot, and within the same schedule, is new. The results may inform new approaches to immunisation against other diseases, he said.

The study also found that a first dose of the AstraZeneca-Oxford vaccine followed by any of the other candidates in the study generated a particularly robust response, consistent with findings in June.

The study was designed as a so-called “non-inferiority” study – the intent is to demonstrate that mixing is not substantially worse than the standard schedules – and compares the immune system responses to the gold- standard responses reported in previous clinical trials of each vaccine.

Study details

Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial

Arabella Stuart, Robert Shaw, Xinxue Liu, Melanie Greenland, Parvinder Aley, Prof Nick Andrews, J C Cameron, Sue Charlton, Elizabeth Clutterbuck, Andrea Collins, Tom Darton, Tanya Dinesh, Christopher Duncan, Anna England, Prof Saul Faust,
Prof Daniela Ferreira, Prof Adam Finn, Anna Goodman, Christopher A Green,
Bassam Hallis, Prof Paul T Heath, Helen Hill, Bryn M Horsington, Prof Teresa Lambe,
Rajeka Lazarus, Prof Vincenzo Libri, Patrick J Lillie, Yama F Mujadidi, Ruth Payne, Emma L Plested, Samuel Provstgaard-Morys, Maheshi N Ramasamy, Mary Ramsay, Prof Robert C Read, Hannah Robinson, Prof Gavin R Screaton,
Nisha Singh, David Turner, Paul Turner, Iason Vichos, Rachel White,
Prof Jonathan S Nguyen-Van-Tam, Matthew D Snape.

Published in The Lancet on 6 December 2021

Summary

Background
Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer–BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax).

Methods
Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311.

Findings
Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation.
Interpretation

Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification.

 

Reuters article – Mixing Pfizer, AstraZ COVID-19 shots with Moderna gives better immune response -UK study (Open access)

 

The Lancet article – Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial (Open access)

 

See more from MedicalBrief archives:

 

COVID antibody levels boosted sixfold with mixed AstraZeneca-Pfizer shot

 

J&J vaccine: Booster jabs from Moderna or Pfizer might be better – NIH trial

 

CDC panel backs third Pfizer and Moderna shot for the immunocompromised

 

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