In a recent study posted to the medRxiv* preprint server, researchers estimated the impact of different coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) booster vaccinations in the United States (US) during fall 2022.
The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants of concern (VOCs) warrants the development of adapted SARS-CoV-2 vaccines as health authorities and policy-makers plan for COVID-19 vaccinations in fall 2022. Studies have reported that COVID-19 patients elicit lower neutralizing antibody (nAb) titers against the SARS-CoV-2 Omicron BA.4/5 VOC than against Omicron BA.1 VOC.
About the study
In the present study, researchers estimated the prevention of SARS-CoV-2 infections and associated hospitalizations by administering three different mRNA vaccine boosters against SARS-CoV-2 over six months (between September 2022 and February 2023) among adults residing in the US.
The participants were boosted with the mRNA-1273 monovalent vaccine (ancestral strain) from September 2022, the mRNA-1273.214 bivalent vaccine (ancestral strain + Omicron BA.1) from September 2022 onwards, or the mRNA-1273.222 bivalent vaccine (ancestral strain + Omicron BA.4/5) from November 2022. In addition, sensitivity analyses were performed based on SARS-CoV-2 transmissibility, mRNA vaccination coverage, masking, Paxlovid (nirmatrelvir/ritonavir) treatment, and antibody waning against SARS-CoV-2 over time.
Susceptible-exposed-infection-recovered (SEIR) compartmental modeling was used for the analysis stratified by age and SARS-CoV-2 transmission dynamics. The SIER model was calibrated between 31 January 31, 2020, and 31 May 2022 for matching all SARS-CoV-2 infections to IHME (institute for health metrics evaluation) estimates.
Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning of natural and vaccine-induced immunity changed the magnitude of cases prevented but boosting with mRNA-1273.214 in September consistently prevented more cases of infection and hospitalization than the other two strategies.
It was assumed that the prime vaccinations for the study participants were combinations of the BNT162b2 and AD26.COV2.S and mRNA-1273 vaccines and that all participants received prime vaccinations and initial booster vaccinations before 31 May 2022, and the second booster vaccinations before 15 June 2022.
The model simulation period was divided into three timeframes: pre-Omicron (between 31 January 2020 and 30 November 2021); Omicron BA.1/2 (between 1 December 2021 and 14 August 2022); and Omicron BA.4/5 (between 15 August 2022 and 28 February 2023). Vaccine effectiveness (VE) was estimated for prime vaccinations, the first booster, and the second booster based on relative nAb titers [geometric mean titers (GMT)] for estimating the impact of vaccinations and newly emerging SARS-CoV-2 variants.
Compared to no boosters, the estimated decreases in SARS-CoV-2 infections by mRNA-1273, mRNA-1273.214, and mRNA-1273.222 vaccines were 34%, 40%, and 18%, respectively, over six months. Likewise, initiating booster vaccinations in September viz. mRNA-1273 and mRNA-1273.214, significantly prevented hospitalizations by 42% and 48%, respectively, than booster vaccination initiation in November by mRNA-1273.222 (25%) over six months in comparison to no boosters.
The model predicted that by September 2022, individuals who received only prime vaccinations or the first booster would elicit no vaccine-induced immunity, while VE for the second booster was <30%, and VE against COVID-19 severity was <50% for recipients of only prime vaccinations. The mRNA-1273.214 booster increased protection against SARS-CoV-2 by 70% and against infection severity by 90%.
If it is assumed that Omicron BA.4/5 would persist for >1 year, the mRNA-1273, mRNA-1273.214, and mRNA-1273.222 boosters were estimated to decrease SARS-CoV-2 infections by 36%, 47%, and 45%, respectively, in comparison to booster vaccinations in the fall period. The projected COVID-19 case counts were estimated to decrease with stronger natural immunity; however, the mRNA-1273.214 booster remained effective even after assuming that natural immunity waned at a rate of 50% with a 36% decrease in COVID-19 case counts in comparison to no boosters in the fall period.
The percent reduction in six months of COVID-19 cases when boosting with mRNA-1273.214 was 33%, and no fall booster was 36%. On delaying the enhancement in SARS-CoV-2 transmissibility from 15 August to 15 September 2022 and administering boosters from September onwards, the reduction in infection severity with mRNA-1273.214 in comparison to no fall booster was 42%.
If fall booster uptake was 25% of the estimated base case scenario, the estimated reductions in COVID-case counts were 27%, 14%, and 32% for the mRNA-1273, mRNA-1273.222, and mRNA-1273.214 boosters, respectively. Reducing the rate of antibody waning of the mRNA-1273.214 booster by 25% prevented 41% of infections, 50% prevented 42% of infections, and 75% prevented 43% of SARS-CoV-2 infections, respectively, in comparison to no fall booster.
Overall, the study findings showed that vaccinating with the bivalent mRNA-1273.214 booster was more effective over six months in preventing Omicron BA.4/5 infections and associated hospitalizations compared to the next-generation mRNA-1273.222 vaccine only because mRNA-1273.214 booster could be administered two months earlier than the mRNA-1273.222 booster. Booster vaccinations must not be delayed until an Omicron BA.4/5-specific vaccine is available.
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.
- Kohli, M. et al. (2022) “The Potential Clinical Impact of Implementing Different COVID-19 Boosters in Fall 2022 in the United States”. medRxiv. doi: 10.1101/2022.07.19.22277824. https://www.medrxiv.org/content/10.1101/2022.07.19.22277824v1