Effectiveness of monovalent COVID-19 mRNA booster vaccination vs. two-dose primary series during Omicron variant circulation

In a recent study published in Influenza and other respiratory viruses, researchers estimated the immune protection conferred by monovalent-type coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) booster doses vs. two-dose prime vaccination series during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant predominance in community settings.

Study: Effectiveness of first and second COVID-19 mRNA vaccine monovalent booster doses during a period of circulation of Omicron variant sublineages: December 2021–July 2022. Image Credit: PIC SNIPE/Shutterstock


For United States (US) residents, COVID-19 vaccine boosters have been extended to young individuals over concerns of waning immunity to improve immune protection against Omicron, the continuous evolution of which has threatened COVID-19 vaccine effectiveness (VE). Second booster doses have been recommended for adults immunocompromised or aged above 50. However, concerns over adverse effects and VE have contributed to COVID-19 vaccine reluctance in the US.

About the study

In the present study, researchers evaluated the relative vaccine effectiveness of COVID-19 mRNA boosters vs. complete prime vaccinations among community residents with active COVID-19 surveillance in the US.

The study comprised the prospective assessment of coronavirus disease 2019 in the community (PACC) trial participants, followed from 20 December 2021 to 28 June 2022, aged ≥5.0 years, and who were provided care by the Marshfield clinic health system (MCHS). Surveys were distributed at recruitment to obtain data on age, gender, and comorbidities.

SARS-CoV-2 vaccination data were obtained from the MCHS electronic medical records, the Immunization Registry of Wisconsin, and t   vaccination cards of the participants. Serum samples were obtained at recruitment (between November 2020 and March 2021), at intervals of 12.0 weeks (between January 2021 and June of the same year), and at 24.0 0 weeks (between April and September 2021) post-recruitment. In addition, sera were obtained between February and May 2022, and after 12.0 weeks, between May and July 2022.

The relative VE of second boosters (fourth dose) vs. single booster (third dose) was estimated among individuals aged ≥50 years, who were followed between 29 March 2022 and 28 July 2022 and were eligible for the second booster ≥4.0 months post first booster receipt. Cox proportional hazards modeling was performed for the analysis, and the hazard ratios (HRs) were calculated, with data adjustments for prior COVID-19 history and age.

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Participants completed weekly symptom surveys, and nasal swabs were collected by self or parents when individuals developed ≥1.0 respiratory symptoms such as cough, fever, sore throat, smell loss, taste loss, muscle and/or body ache, diarrhea, or breathlessness. SARS-CoV-2 was detected in the specimens using reverse transcription polymerase chain reaction (RT-PCR).

In addition, COVID-19 was diagnosed based on the presence of antibodies against SARS-CoV-2 spike (S) protein, S receptor-binding domain, or nucleocapsid (N) protein using enzyme-linked immunosorbent assays (ELISA). SARS-CoV-2 strain proportions were assessed using the global initiative on sharing all influenza data (GISAID) database data. The team excluded individuals who received prime doses of Ad26.COV2.S (46 individuals) vaccines or mixed messenger ribonucleic acid vaccines (one individual). The monovalent vaccines encoded for the SARS-CoV-2 ancestral strain.


The analysis comprised 883 individuals with a median age of 55 years, among whom 61.0% were women, and 56.0% had comorbidities. Among the participants, 29% (n=258) of individuals were fully vaccinated, and 71% (n=625) of individuals were booster-vaccinated. Among boosted COVID-19 vaccinees, 61% (n=384) and 39% (n=241) received prime doses of BTN162b2, and mRNA-1273, respectively, and 65% and 35% received booster doses of the corresponding vaccines, respectively.

Among the participants, 59% (n=239) and 41% (n=-168) received one and two booster doses, respectively. Relative VE was 51.0% favoring boosters over prime vaccinations, and showed no significant variation with prior COVID-19 history. Relative VE estimated were 74.0% at 15.0 days to 90.0 days following booster doses, reducing to 42.0% after 91.0 to 180.0 days, and 36.0% after 180.0 days. The relative VE for the second booster vs. the first booster was 24.0%.

Among the participants, 25% (n=219) developed reinfections, of which 97 (28/10,000 individual-days) occurred following primary vaccinations and 122 following booster vaccinations (12/10,000 individual days). The relative VE estimates did not vary significantly by age, albeit lower point estimates for individuals aged 5.0 to 17.0 years and ≥50.0 years. VE estimates for only individuals aged 18 to 49 years were significant. Reinfections were documented among 10% (n=20) of booster-vaccinated and 25% (n=33) of prime-vaccinated individuals without prior COVID-19 history.

Relative VE estimates remained unaltered after excluding 54 immunocompromised individuals. Relative VE of the booster dose vs. primary doses reduced with increasing duration from booster dose receipt. Compared to prime-vaccinated and non-boosted individuals, the relative VE estimated was the greatest (74%) at 15.0 to 90.0 days following booster dose receipt. The risk of COVID-19 did not vary significantly among single-booster and double-booster recipients.


Overall, the study findings showed that COVID-19 mRNA vaccine boosters conferred significant immune protection against COVID-19, although the protective immunity waned with time. However, the second booster dose did not add significant immune protection among individuals aged ≥50.0 years. Healthcare authorities must encourage bivalent booster dose uptake to improve protection against Omicron BA.4/ 5 subvariants.

Journal reference:
  • Petrie, JG, King, JP, McClure, DL, et al. Effectiveness of first and second COVID-19 mRNA vaccine monovalent booster doses during a period of circulation of Omicron variant sublineages: December 2021–July 2022. Influenza Other Respi Viruses. 2023; 17(3):e13104. doi: 10.1111/irv.13104

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antibodies, Coronavirus, Coronavirus Disease COVID-19, Cough, covid-19, Diarrhea, Electronic Medical Records, ELISA, Enzyme, Evolution, Fever, Healthcare, immunity, Immunization, Influenza, Muscle, Omicron, Polymerase, Polymerase Chain Reaction, Protein, Receptor, Respiratory, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Sore Throat, Syndrome, Throat, Transcription, Vaccine

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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