Efficacy and durability of BNT162b2 vaccine against Omicron substrains in South Africa

To the editor:

Data are limited on the efficacy of the BNT162b2 vaccine (Pfizer-BioNTech) against the BA.4 and BA.5 sublines of the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that led to the wave. The last fifth of the infection in South Africa.1 We previously reported a vaccine efficacy of 70% after two doses of BNT162b2 vaccine against severe disease during the fourth wave of Omicron infection driven by the BA.1 substrain in South Africa.1,2

In this analysis, we evaluated the efficacy and durability of the BNT162b2 vaccine separately against BA.1 or BA.2 and against BA.4 or BA.5 among members of Discovery Health, a medical care organization that provides health insurance to 3.7 million people in South Africa. During the period from 15 November 2021 to 24 June 2022, a total of 32,883 patients hospitalized for medical treatment underwent PCR testing for SARS-CoV-2, a period that extended to BA.1-omicron waves BA.2 and BA. 4-BA.5. Of these patients, 5909 (18.0%) were found positive for SARS-CoV-2 (Table S4 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).

In this population, we evaluated the efficacy of two and three doses (that is, the original two-dose series plus a booster dose) of BNT162b2 vaccine against hospitalization for the treatment of potential sequelae of coronavirus disease 2019 (Covid-19) according to whether the BA sublines .1 and BA.2 are dominant (from November 15, 2021 to February 28, 2022) or whether sublines BA.4 and BA.5 are dominant (from April 15 to June 24, 2022).1

We applied a negative test design and data exclusion rules to obtain estimates of vaccine efficacy. In this analysis, we used a logistic regression model after adjusting for covariates to estimate vaccine efficacy as 1 minus vaccination odds among positive cases. Vaccination status was analyzed according to the time elapsed since the last dose of vaccine was administered (not vaccinated, 0 to 13 days, 14 to 27 days, 1 to 2 months, 3 to 4 months, 5 to 6 months, 7 to 8 months or 9 months).

Efficacy of the BNT162b2 vaccine against hospitalization for Covid-19 in South Africa, according to the dominant Omicron sub-strain.

Among patients who received two doses of the vaccine, diminished efficacy against hospitalization was evident as early as 3 to 4 months post-vaccination during both periods when omicron subtypes predominated. Vaccine efficacy was 56.3% (95% confidence interval [CI]51.6 to 60.5) during wave BA.1-BA.2 and 47.4% (95% CI, 19.9 to 65.5) during wave BA.4-BA.5 (Table 1). Although booster with a third dose maintains vaccine efficacy against severe disease caused by all four subspecies at 1-2 months, vaccine efficacy decreased from 3 to 4 months to 50.0% efficacy (95% CI, 4.4 to 73.9) During wave BA.1 – BA.2 and 46.8% (95% CI, 35.3 to 56.2) during wave BA.4-BA.5.

Thus, after two or three doses of BNT162b2 vaccine, we found a rapid decrease in vaccine efficacy against current substrains of the omicron variant with respect to protection against hospitalization. Our data indicate that booster maintains vaccine efficacy against severe disease caused by current sub-strains of Omicron, although evidence of rapidly diminishing robustness indicates the need for regular booster as early as 4 months after the last dose or the need for vaccines. To include variables of anxiety to maintain protection.

Shirley Cooley, BA
Jeren Naiger, BA.
Discovery Health, Sandton, South Africa

Leslie Bamford, MB, Ch.B.
National Department of Health, Pretoria, South Africa

Linda Jill Baker, MB, CHB, Ph.D.
Desmond Tutu HIV Foundation, Cape Town, South Africa

Matt Zilstra, BA.
Discovery Health, Sandton, South Africa

Glenda Gray, MB, B.
South African Medical Research Council, Cape Town, South Africa
[email protected]

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This message was published on September 14, 2022, in NEJM.org.

Efficacy of the BNT162b2 vaccine against hospitalization for Covid-19 in South Africa, according to the dominant Omicron sub-strain.*

Time Elapsed Since the Last Vaccine Dose VE for dose 2 VE for dose 3
BA.1-BA.2 Omicron Wave BA.4 – BA.5 Omicron Wave BA.1-BA.2 Omicron Wave BA.4 – BA.5 Omicron Wave
percent (95% CI)
0 to 13 days 66.7 (38.3–82.0)
14-27 days 80.3 (62.8 – 89.5) 81.6 (68.1-89.4)
1-2 months 61.3 (54.7 – 66.9) 66.4 (53.7-75.6) 68.8 (59.5–76.0)
3-4 months 56.3 (51.6-60.5) 47.4 (19.9-65.5) 50.0 (4.4 – 73.9) 46.8 (35.3-56.2)
5-6 months 45.6 (39.3-51.3) 26.3 (7.1–41.6)
7-8 months 38.4 (16.9 – 54.4) 23.6 (11.1–34.3)
≥9 months 19.3 (6.3-30.5)