COVID-19 Update #128 4/22/2022

COVID-19 Vaccines
 
Pfizer and BioNTech announced immunology data from a 140 patient, Phase II/III trial, where a booster dose of their COVID-19 vaccine, given six-months after the initial series, produced a six-fold increase in antibodies one month after the booster compared to antibody titers one month after the second dose in children 5 through 11 years of age. A sub-analysis of 30 patients found that the Omicron variant was neutralized by the antibodies. 
 
A pre-print draft describes an 895 patient, open-label, Phase II/III trial, where a bivalent COVID-19 vaccine developed by Moderna was tested against its approved vaccine. The bivalent vaccine consisted of the original vaccine with the addition of mRNA for the Beta variant spike proteins. Compared to original vaccine, the bivalent vaccine elicited increased antibody titers for the original virus and Beta, Omicron and Delta variants after 28 days. Antibody titers levels were still elevated for the bivalent vaccine at 180 days for the original Beta, Omicron variants. The bivalent vaccine was given as a booster about nine months after the primary series. Moderna is also developing a bivalent vaccine that combines the original vaccine with mRNA for the Omicron variant spike proteins. A blinded randomized trial for this vaccine will be reported in 2Q22. Moderna feels the Omicron bivalent vaccine will be chosen for use as a booster in the fall.
 
A systematic review and meta-analysis of 29 studies involving 11,713 solid organ transplant patients identified risk factors for decreased antibody titers. The risk factors included older age, recent transplantation, deceased donor status, active use of antimetabolites, and recent exposure to antithymocyte globulin or rituximab. Receiving additional doses of an mRNA vaccine increased the chance of developing higher antibody titers.
 
British researchers analyzed the vaccine effectiveness (VE) for the Omicron variant for COVID-19 vaccines from Pfizer-BioNTech and AstraZeneca. 

• After five months, VE was non-existent for two doses of the AZ vaccine and had dropped to under 9% after six months for two doses of the Pfizer-BioNTech vaccine.
• When a Pfizer-BioNTech vaccine was used as a booster for AZ vaccine patients, VE was 62% after four weeks and 39.6% after 10 weeks.
• When Pfizer-BioNTech vaccine patients received a booster with the same vaccine, VE was 67% after four weeks and 46% after 10 weeks.
• When a Moderna vaccine was used as a booster for AZ vaccine patients, VE was 70% after four weeks and 61% after 10 weeks.
• When Pfizer-BioNTech vaccine patients received a booster with the Moderna vaccine, VE was 74% after four weeks and 64% after 10 weeks.

Novavax announced that in a 642 patient, Phase I/II trial (NCT04961541), immunization with two doses of a COVID-19/Influenza combination vaccine, given 56-days apart, elicited antibody levels similar to levels seen with an individual COVID-19 or Influenza vaccine in Australian patients who were previously vaccinated with a COVID-19 vaccine or recovered from COVID-19.
 
COVID-19 Antibodies
 
In the six-month, 5,197 patient, Phase III, PROVENT trial (NCT04625725), 0.3% of patients who received a prophylactic dose of tixagevimab plus cilgavimab developed symptomatic COVID-19 compared to 1.8% who received placebo in adults at increased risk of an inadequate response to COVID-19 vaccination.