In a recent study published in Nature Communications, a team of researchers from Canada investigated the efficacy of booster doses of the monovalent messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccine in preventing hospitalization and death during the dominance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.
Study: Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes. Image Credit: Billion Photos/Shutterstock
Background
The SARS-CoV-2 Omicron variant carries novel mutations in the spike protein region that increase its transmission and ability to escape the neutralizing antibodies elicited by COVID-19 vaccines. Various Omicron subvariants have emerged and circulated since late 2021, with BA.1 and BA.2 being predominant until June 2022 and then replaced by BA.4 and BA.5.
Amidst concerns about the waning of vaccine-induced immunity, booster doses of COVID-19 vaccines were offered to all adults in Ontario, Canada, by December 2021. This was expanded to a fourth booster dose for adults above 60 by April 2022 and to all adults by July of the same year. While bivalent mRNA vaccines that encode the spike protein of the ancestral SARS-CoV-2 strain and the Omicron variant have been introduced in Canada, the monovalent vaccines continue to be the vaccines that are administered the most.
Furthermore, while the seroprevalence of the general population in Ontario has increased during the dominance of the Omicron variant, the relative seroprevalence of the older population above the age of 60 remains low. Therefore, it is important to understand whether monovalent mRNA COVID-19 booster vaccines effectively prevent severe outcomes to plan future booster regimens and vaccine development.
About the study
The present study used a test-negative design while analyzing datasets of SARS-CoV-2 laboratory testing in Ontario, health administration, and COVID-19 vaccination and surveillance.
The study included adults above 50 with more than one SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test between January and October 2022. Individuals who were immunocompromised or had received the bivalent mRNA vaccine or the non-replicating viral vector vaccines Ad26.COV2 and ChAdOx1-S were excluded from the study.
Most positive test results by the end of January 2022 were due to Omicron infections. Any infections with the Delta variant were identified based on the spike gene target sequencing or whole genome sequencing and excluded. Furthermore, about 95% of the individuals had received the BNT162b2 or mRNA-1273 mRNA vaccines for all doses.
The investigated outcomes were hospitalization or death due to COVID-19. The controls were individuals who were symptomatic but had negative SARS-CoV-2 tests, with or without severe outcomes.
The number of monovalent mRNA COVID-19 vaccine doses received and the time elapsed since the most recent dose were used to classify the participants. For individuals who received two, three, and four doses of the vaccine, the outcomes were examined for more than 300, 240, and 120 days after vaccination, respectively.
Results
The results indicated that the vaccine effectiveness was between 91% and 98% between one week and two months after the third dose (first booster dose), which then waned to between 76% and 87% after 240 days or more. However, a fourth booster dose restored the vaccine effectiveness levels to between 92% and 97% for two months following the fourth dose, which waned to between 86% and 89% after 120 days or more.
The findings indicated that during the dominance of the BA.4/BA.5 Omicron subvariants, the vaccine effectiveness was lower and waned faster than the vaccine effectiveness during the predominance of the BA.1 and BA.2 subvariants, especially after 120 days. The authors believe that the reduced vaccine effectiveness and rapid waning of immunity against the BA.4/BA.5 subvariants are most likely due to the greater immune evasive abilities of these subvariants.
While the study indicated that booster doses of the monovalent mRNA vaccines grant older adults strong protection against severe outcomes such as hospitalizations and death due to Omicron infections, the rate of waning of immunity beyond four months remains unclear.
Furthermore, given the lower effectiveness against the BA.4/BA.5 subvariants, the researchers believe that the effectiveness of the vaccine-induced immunity from the monovalent mRNA vaccines could be further reduced against newly emergent subvariants such as XBB and BQ.1.1. Therefore, adherence to disease mitigation measures such as improved ventilation and wearing of face masks needs to be continued along with subsequent booster doses.
Conclusions
Overall, the results reported that booster doses of the monovalent mRNA COVID-19 vaccines were effective in granting strong protection to older adults against severe outcomes of Omicron infections for up to four months. However, the vaccine-induced immunity was seen to wane faster against infections with the BA.4/BA.5 subvariants.
Therefore, the authors believe that along with continuing disease mitigating measures and administering booster doses, the vaccine effectiveness against newly emergent Omicron subvariants needs to be consistently monitored.
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