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Currently authorized bivalent COVID-19 boosters demonstrated similar protection against symptomatic illness from the XBB/XBB.1.5 Omicron subvariants as from BA.5-related subvariants, according to a CDC study.

From December 2022 to January 2023, the bivalent boosters' vaccine effectiveness (VE) against symptomatic infection was a similar 48% versus XBB/XBB.1.5-related strains and 52% versus BA.5-related sublineages, reported Ruth Link-Gelles, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and colleagues in (MMWR).

Meanwhile, Pfizer's updated booster demonstrated superior neutralizing antibody activity compared with the company's original product against all the latest Omicron subvariants, including XBB.1, according to Kena Swanson, PhD, of Pfizer Vaccine Research and Development in Pearl River, New York and colleagues, writing in the . Their findings contradict earlier research from other labs that found no significant difference in neutralizing activity with the bivalent over the monovalent vaccine.

According to the from the CDC, XBB.1.5 is responsible for 49.1% of new COVID-19 cases in the U.S., while XBB is responsible for another 3.3%.

CDC Report

While the updated bivalent boosters were designed to target the Omicron BA.4/5 subvariants along with the ancestral strain of SARS-CoV-2, early indicated lower neutralizing activity against XBB compared with other Omicron sublineages, noted Link-Gelles and co-authors, raising concerns about a potential reduction in VE.

In order to estimate the VE of the bivalent COVID-19 boosters against BA.5-related and XBB/XBB.1.5-related illness, the team used the Increasing Community Access to Testing national pharmacy program for SARS-CoV-2 testing. Their analysis included immunocompetent adults who had previously received at least two doses of the original monovalent COVID-19 vaccines.

Reduction or failure of spike gene (S-gene) amplification in real-time RT-PCR tests served as a proxy for a likely infection with BA.5-related sublineages while presence of S-gene target served as a proxy for likely infection with XBB/XBB.1.5-related sublineages.

Among 29,175 test results from people with COVID-like illness from Dec. 1, 2022 to Jan. 13, 2023, nearly half (47%) were positive for SARS-CoV-2. Of these, 78% of these showed failure or reduction of the S-gene, indicating they were BA.5-related; while the rest contained presence of the S-gene, indicating they were likely XBB/XBB.1.5-related.

When the CDC researchers broke down VE by age group, protection against symptomatic illness from BA.5- and XBB/XBB.1.5-related sublineages tended to be higher among younger individuals:

• 18-49 years: 52% and 49%, respectively
• 50-64 years: 43% and 40%
• 65 and older: 37% and 43%

"Findings from this study suggest that bivalent booster doses are continuing to provide additional protection against symptomatic infection for at least the first 3 months after vaccination in persons who had previously received 2, 3, or 4 monovalent vaccine doses, which supports recommendations to continue to increase bivalent booster coverage," the study authors concluded.

Another released on Wednesday further explains how S-gene target amplification is being used to monitor for emerging variants.

Pfizer Neutralization Data

Swanson's group compared neutralizing antibody titers against the wild-type SARS-CoV-2 strain and multiple Omicron subvariants in individuals ages 55 and over who received a fourth dose with either Pfizer's BA.4/5-directed bivalent vaccine (n=38) or the company's original monovalent vaccine (n=40).

The researchers collected samples on the day of the fourth dose and 1 month later. The fourth dose was given about 6.6 months after the third dose for monovalent vaccine recipients and about 11 months after the third dose for the bivalent group.

Bivalent vaccine recipients "consistently elicited higher neutralizing 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 infection," according to the researchers.

They noted that vaccine-elicited neutralization was generally lowest with the BA.2.75.2, BQ.1.1, and XBB.1 subvariants, but still, neutralizing titers after the bivalent dose were several times higher for these strains when compared with the company's original vaccine.

Among all participants, the geometric mean factor increases from baseline for the bivalent versus monovalent vaccines were as follows:

• Wild-type: mean factor increase of 5.8 vs 3.0
• BA.4/5: mean factor increase of 13.0 vs 2.9
• BA.4.6: mean factor increase of 11.1 vs 2.3
• BA.2.75.2: mean factor increase of 6.7 vs 2.1
• BQ.1.1: mean factor increase of 8.7 vs 1.8
• XBB.1: mean factor increase of 4.8 vs 1.5

"These data suggest that the bivalent vaccine is more immunogenic than the original vaccine, with greater breadth of responses against circulating Omicron sublineages," Swanson and colleagues concluded.

After the fourth dose, higher neutralizing antibody titers were seen in both groups among those with a history of prior infection, but "the difference between the original and bivalent neutralizing geometric mean factor increase was greater in the serum samples obtained from participants without previous infection than in those obtained from participants with previous infection," the researchers noted.

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