Throughout the study, which the partners described as the yet most comprehensive heterologous booster trial to explore boosting across different primary vaccination types, neutralizing antibodies increased 9-to 43-fold in all age groups. The safety profile was shown to be similar to that of the vaccines it was tested with, including AstraZeneca, Johnson & Johnson, Moderna and Pfizer/BioNTech.

In the first cohort, the four most widely approved Covid vaccines using mRNA and adenovirus vector technologies were boosted with the Sanofi/GSK candidate after full primary vaccination. Trial participants received one 5 µg booster dose of the French-British vaccine targeting the original D614 parent virus between four and ten months after a complete primary vaccination schedule. 

The trial is continuing across sites in multiple countries, including the US, France, and the UK. To address the emergence of variants of concern, additional trial cohorts are assessing the boosting potential of monovalent and bivalent vaccine formulations also containing the Beta (B.1.351) variant. More data are expected during the first half of 2022.

As the Omicron variant was not circulating during the trial, it was not part of any assessment. However, using sera from booster trial participants, Sanofi said testing is underway to establish the ability of the vaccine candidate to cross-neutralize against Omicron.

Prevention of symptomatic Covid-19

In the global Phase 3 trial dubbed VAT0008, in which the primary endpoint is prevention of symptomatic Covid-19 and the second is to prevent severe disease and infection with the virus, Sanofi and GSK are assessing efficacy of a vaccine formulation containing the spike protein against D164. The 10,000 adult participants recruited in the US, Asia, Africa and Latin America are receiving two doses of 10 µg vaccine or placebo at day 1 and day 22. A second stage is evaluating another bivalent formulation, adding the spike protein of the B.1.351 (Beta) variant.

Funded by the US Biomedical Advanced Research and Development Authority (BARDA), the Phase 3 trial includes regular reviews by an independent Data Safety Monitoring Board (DSMB). During its last review, Sanofi said the board identified no safety concerns.

As regulators require Phase 3 efficacy to be demonstrated in populations never infected by the Covid-19 virus, and this study recruited most participants in the 2021 third quarter, which saw significantly increased infection with the Delta variant, the companies have agreed to extend the trial to accrue the number of events needed for analysis. Results are now expected in the 2022 first quarter.

Parallel to these trials, Sanofi said it is continuing to toll-manufacture up to half a billion doses of the BioNTech/Pfizer, Moderna and Johnson & Johnson vaccines. The French pharma stepped in to boost overall output during a phase of short supply that coincided with a phase of disappointing trials with its shot that combines its recombinant antigen with GSK’s adjuvant.

Author: Dede Williams, Freelance Journalist