Long-term protection and high efficacy of bivalent BA.1 booster confirmed in older adults

By Tarun Sai LomteReviewed by Lily Ramsey, LLMApr 5 2023

A recent study published in the medRxiv* preprint server estimated the duration of protection with monovalent vaccination and the efficacy of bivalent vaccine boosters against hospitalization due to coronavirus disease 2019 (COVID-19).

Study: Long-term duration of protection of ancestral-strain monovalent vaccines and effectiveness of the bivalent BA.1 boosters against COVID-19 hospitalisation during a period of BA.5, BQ.1, CH.1.1. and XBB.1.5 circulation in England. Image Credit: GroundPicture/Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Monovalent vaccines based on the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been effective against severe COVID-19.

However, the emergence of mutant variants with immune-evasive properties has attenuated vaccine effectiveness and durability of protection. Several countries have implemented frequent booster programs to protect vulnerable (sub)populations.

Bivalent vaccines targeting ancestral and Omicron spike proteins have been developed. Studies showed that bivalent vaccines increased neutralizing capacity against SARS-CoV-2 Omicron BA.2.75, BA.4, and BA.5.

About the study

In the present study, researchers evaluated long-term protection from monovalent vaccines and the effectiveness of bivalent vaccines against COVID-19-related hospitalization in England. They implemented a test-negative case-control design.

The study periods were June 13 to December 25, 2022, and September 5, 2022, to February 5, 2023, to assess the duration of protection with monovalent vaccines and bivalent booster vaccination efficacy, respectively.

The date of the most recent positive test in the study period(s) was identified. Non-Omicron cases were excluded. COVID-19 testing data were linked to the National Immunization Management System (NIMS).

Data on vaccination, sex, age, ethnicity, risk group status, immunosuppression, clinically extremely vulnerable status, and social/healthcare worker status were accessed from NIMS.

Inpatient admissions for acute respiratory illnesses were identified from the Secondary Uses Service and linked to the testing data.

SARS-CoV-2 tests were restricted to hospitalizations requiring supplemental oxygen, intensive care, or mechanical ventilation to estimate vaccine effectiveness against severe disease outcomes.

Multivariate logistic regression used test results and vaccination as the outcome and primary variable of interest, respectively. The incremental vaccine effectiveness (iVE) of the fourth dose was estimated relative to the last third received at least six months before the sample date in people aged 75 or older.

The iVE of the bivalent booster was estimated in those who were at least double-vaccinated before September 5, 2022, and six months before the test date.

Findings

The authors identified 63,251 tests from hospitalized patients aged 18 or older, including 19,841 cases who did not receive the bivalent booster.

The absolute vaccine effectiveness (aVE) of two (monovalent) doses was 68.8% after three to five months in the 18-64 age group and reduced to 22.2% after 15 months; the aVE of three doses was 46.4% after three to five months and 18.3% after 12-15 months.

In people aged 65 or above, the aVE of two (monovalent) doses was 71.7% after three to five months post-second vaccination and 40.2% after 15 months; the aVE after the third dose was 65.3% after three to five months and 52.3% after 12-14 months.

The aVE against the severe disease was 39.1% after 15 months post-second vaccination and 49.3% after 12-14 months post-third dose. 

Furthermore, The iVE of the fourth dose relative to the third dose in individuals aged 75 or older peaked at 50% and decayed to similar levels as the protection with a waned third dose.

The team identified 49,062 tests from hospitalized patients aged 50 or older who received the bivalent booster. Of these, 9,954 and 39,108 were cases and controls, respectively.

Additionally, The iVE of the bivalent booster peaked at 53% after two to three weeks and declined to 35.9% after ten weeks. No significant differences were observed when stratified by the manufacturer of bivalent booster vaccines.

The iVE against the severe disease was 60.9% and 69.3% for bivalent vaccines from Pfizer and Moderna, respectively.

In addition, The iVE of the bivalent booster vaccination increased with time since the last dose. It was not significantly different between those who received two, three, or four doses before bivalent vaccination. The iVE of the bivalent booster in people aged 75 or older was 48% after two to four weeks.

Conclusions

The study revealed that protection with monovalent vaccine doses against hospitalization was long-lasting and plateaued around six months after the last vaccination, with modest protection at 15 months or later.

The bivalent booster incremented protection to approximately 53% relative to that with monovalent vaccines.

Together, the findings provide evidence of long-lasting protection against severe disease after three or more doses of monovalent vaccines, suggesting that additional doses may not be required for people not at risk of severe outcomes.

Further, the bivalent booster conferred additional protection in older individuals at risk of severe disease.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.