Covid-19 Living Data

Trial NCT05124171; EudraCT 2021-004550-33
Publication Launay O, N Engl J Med, 2022
Dates: 2021-12-08 to 2022-01-14
Funding: Mixed (From letter to editor: Supported by the French Ministries of Solidarity and Health and of Higher Education, Research, and Innovation. From preprint: French Ministries of Solidarity and Health and Research and Sanofi.)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / France Follow-up duration (months): 0.5
	MV D614 (n = 85) MV B.1.351 (n = 80) BNT162b2 (n = 82)
Inclusion criteria	Adults aged 18 years and older in good health or with stable health if there was a pre-existing medical history previously received two doses of BNT162b2 with an interval of 3 to 6 weeks and the second dose administered between 3 and 7 months prior to the administration of the study booster dose.
Exclusion criteria	Pregnancy or breastfeeding acute febrile infection within the previous 72 h presenting symptoms suggestive of COVID-19 within the previous 28 days having been in contact with an infected individual for the last 14 days before the inclusion visit virologically documented history of COVID-19 (PCR or serology) use of immunosuppressive medications or any immunosuppressive condition that may reduce the immune response history of severe post-vaccination allergic manifestations or a history of allergic reaction at the time of the first vaccine injection having received BCG (tuberculosis) vaccine within the previous year or another vaccine within two weeks prior to the boost injection or scheduled to receive a licensed vaccine within 2 weeks after the boost injection.
Interventions
	Intervention 1 IM dose of MV D614 booster between 3 and 7 months after second BNT162b2 vaccine 1 IM dose of MV B.1.351 booster between 3 and 7 months after second BNT162b2 vaccine
	Control 1 IM dose of BNT162b2 booster between 3 and 7 months after second BNT162b2 vaccine
Participants
	Randomized 247 participants
	Characteristics of participants Type of participants: Adults including healthy or stable co-morbidities N=247 135 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-73
	Description of participants Adults in good health or with stable co-morbidities with no history of COVID-19 in 11 centres in France.
Primary outcome
	In the register Rate of neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains [Time Frame: 15 days]: Increased rate of at least 10 fold between D0 and D15 after the booster dose in neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains, measured by a microneutralisation technique in each group to assess the immunogenicity of a booster dose of an adjuvanted subunit vaccine (SP vaccine) as between D614 or B.1.351 and a mRNA vaccine (Pfizer BioNTech) in adults who were primarily vaccinated with 2 doses of mRNA vaccine (Pfizer BioNTech) with the 2nd dose of vaccine received at least 6 months +/- 1 month prior to the booster dose.
	In the report Percentage of participants who had an increase in the neutralizing-antibody titer by a factor of at least 10 between day 0 and day 15 after receipt of the booster as measured by microneutralization against the original D614 (wild-type) strain of SARS-CoV-2 or the B.1.351 (beta) variant.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: No Data accessibility: Corresponding author Odile Launay, M.D., Ph.D.: odile.launay@aphp.fr
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article and its supplement, the preprint, study registry and protocol were used in data extraction and risk of bias assessment. Preliminary analysis, follow-up is ongoing; data reported herein up to 15 days after booster. The target sample size (N=300) specified in the protocol was not achieved (N=247). Unsolicited adverse events were not reported. Cellular response in the registry was not reported in the paper. There is no change from the trial registration in the intervention and control treatments.