Bivalent Covid-19 vaccines provide significantly better protection – an edge in efficacy of around 37 percentage points – than their monovalent counterparts against severe disease and death from infections caused by Omicron sub-variants, data from two recent reports published in the New England Journal of Medicine (NEJM) show.
Bivalent vaccines are shots that include a component of the original Sars-Cov-2 strain to provide broad protection against the viral disease with an added component of the current Omicron sub-variants in circulation in an attempt to offer wider protection against the disease.
“Vaccine effectiveness against severe infection resulting in hospitalisation or death was 24.9%… for one monovalent booster dose and 61.8%… for one bivalent booster dose; the difference in vaccine effectiveness against this outcome between the bivalent booster and the monovalent booster was 36.9 percentage points…,” NEJM said in a report titled ‘Effectiveness of Bivalent Boosters against Severe Omicron Infection’, which was published on Wednesday.
To be sure, when looking at efficacy numbers from vaccines in such reports it is important to note that they compare hospitalisation/death rates between the types of vaccines, and that hospitalisations in most countries across the world have largely been at record lows thanks to hybrid immunity among masses. In the study cited above, for context, of the 5.9 million non-boosted people who were analysed, only 1,807 needed hospitalisation. Of the over 292,000 people who were given monovalent vaccines, only 61 needed hospitalisation, and 1 million who had bivalent vaccines, only 57 were hospitalised, data shows.
Studies have also shown that immunity gained from a vaccine shot typically wanes in four to six months. This was observed in the NEJM report as well, which said booster effectiveness “peaked at approximately 4 weeks and waned afterwards”.
“We obtained similar vaccine effectiveness estimates when the analysis was restricted to participants who were 18 years of age or older or 65 years of age or older, to participants who received an mRNA vaccine as their primary vaccine, or to previously uninfected participants… In addition, estimates of vaccine effectiveness were similar for the Moderna and Pfizer–BioNTech boosters and similar among the first, second, and third booster doses,” it said.
“Neutralisation of BA.4–BA.5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent Vaccine”, the other report in the journal, compares neutralising activity of monovalent and bivalent vaccines.
Over the past year, new Omicron sub-lineages, including those that have descended from more transmissible BA.2 and BA.4–BA.5, have emerged. These sub-lineages include BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, which are being reported from almost every country around the world.
The experts in the second report compared neutralisation activity against these Omicron sub-lineages in persons who had received three doses of BNT162b2 (Pfizer-BioNTech) vaccine and then received a fourth dose of either the original vaccine or the bivalent BA.4–BA.5 booster.
“Among all the participants, the fourth dose of monovalent BNT162b2 vaccine induced a geometric mean factor increase (i.e., an increase from the day of the fourth dose to one month after the fourth dose) in titers of 3.0 against WT; 2.9 against BA.4–BA.5; 2.3 against BA.4.6; 2.1 against BA.2.75.2; 1.8 against BQ.1.1; and 1.5 against XBB.1; the bivalent vaccine induced neutralizing geometric mean factor increases of 5.8, 13.0, 11.1, 6.7, 8.7, and 4.8, respectively,” read the second report.
The conclusions that the experts reach in the report include that the bivalent BA.4–BA.5 vaccine consistently elicited higher neutralising responses against BA.5-derived sublineages (BA.4.6, BQ.1.1, and XBB.1) and the BA.2-derived sublineage (BA.2.75.2) than the original BNT162b2 vaccine when administered as a fourth booster dose, regardless of the participants’ history of Sars-Cov-2; and after the fourth dose, higher neutralising titers developed in participants with a history of Sars-Cov-2 infection than in those without a history of infection.
Eric Topol, US-based physician-scientist, who earlier arrived at similar conclusion based on the available data, said that these new reports affirmed what most experts already believed.
“A couple of weeks ago I reviewed the BA.5 bivalent booster data and concluded it has worked better than expected today there are three new reports that strongly reinforce that 1. Comparing bivalent vs original for protection vs hospitalizations & deaths,” Topol tweeted in response to the first NEJM report.
“Superior neutralising antibodies vs the new variants with marked immune evasion: XBB.1, BQ.1.1, BA.2.75 compared with the original booster (adds to 12 lab studies),” read another tweet regarding the second report.
US Food and Drug Administration (FDA) authorised the Moderna and Pfizer-BioNTech bivalent Covid-19 vaccines for emergency use as a booster shot at least two months post primary vaccination or having taken a booster dose.
Each of the vaccines contains equal amounts of mRNA encoding the spike protein from the ancestral strain and the spike protein from the BA.4 and BA.5 strains of the B.1.1.529 (Omicron) variant.
Since September 1, these two bivalent mRNA vaccines have replaced their monovalent counterparts as booster doses for persons 12 years of age or older in the United States and in other countries.
“Bivalent boosters provided substantial additional protection against severe omicron infection in persons who had previously been vaccinated or boosted, although the effectiveness waned over time. The effectiveness of bivalent boosters was higher than that of monovalent boosters,” experts had concluded in the report.
