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. 2022 Dec 19;75(12):2088-2096.
doi: 10.1093/cid/ciac345.

Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial

Xuan Ying Poh  1 , Chee Wah Tan  2 , I Russel Lee  1 , Jean-Marc Chavatte  1   3 , Siew-Wai Fong  4 , Tessa Prince  5 , Catherine Hartley  5 , Aileen Y Y Yeoh  2 , Suma Rao  1   6 , Po Ying Chia  1   6   7 , Sean W X Ong  1   6 , Tau Hong Lee  1   6 , Sapna P Sadarangani  1   6   7 , Ray J H Lin  1   6 , Clarissa Lim  1 , Jefanie Teo  1 , Daniel R X Lim  1   3 , Wanni Chia  2 , Julian A Hiscox  4   5 , Lisa F P Ng  4   5   8 , Ee Chee Ren  8   9 , Raymond T P Lin  1   3 , Laurent Renia  4   7   10 , David Chien Lye  1   6   7   8 , Lin-Fa Wang  2 , Barnaby E Young  1   6   7
Affiliations
Free PMC article

Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial

Xuan Ying Poh et al. Clin Infect Dis. .
Free PMC article

Abstract

Background: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown.

Methods: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28.

Results: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated.

Conclusions: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals.

Clinical trials registration: NCT05142319.

Keywords: COVID-19 vaccine booster; Omicron; humoral immunity; live virus neutralization.

Conflict of interest statement

Potential conflicts of interest. B. E. Y. reports personal fees from AstraZeneca, Gilead, Roche, Sanofi, and Novacyte outside the submitted work and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Gilead, Roche, and Sanofi, all paid to institution. C. W. T., L.-F. W., and W. Chia report the following issued patent: US patent 11 054 429 B1, SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein binding. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Consort flow diagram. Abbreviations: BBB, BNT162b2- BNT162b2- BNT162b2; BBM, BNT162b2-BNT162b2-mRNA-1273; D28, day 28; mRNA, messenger RNA.
Figure 2.
Figure 2.
Level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike receptor-binding domain antibody in participants (A) aged <60 years, (B) participants aged ≥60 years, and (C) overall. Participants in the older age group (≥60 years old) who received a heterologous coronavirus disease 2019 vaccine booster (BBM) had significantly higher anti–SARS-CoV-2 immunoglobulin G antibodies than those who received a homologous messenger RNA booster (BBB) at days 7 and 28 post-vaccination. Data analyzed using the Student t test to compare the log10 anti-spike titer. Box represents 25th and 75th percentile, line is median, with whiskers denoting extremes. *P < .05, **P < .01. Abbreviations: BBB, BNT162b2- BNT162b2- BNT162b2; BBM, BNT162b2-BNT162b2-mRNA-1273; CI, confidence interval.
Figure 3.
Figure 3.
Level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 and variants of concern in participants (A) aged <60 years, (B) participants aged ≥60 years, and (C) summary data for Omicron. Level of percent inhibition was determined using a multiplex surrogate virus neutralization test as previously described [8]. Data analyzed using the Mann–Whitney U test. Red dotted line indicates inhibition of 30% (nominal “seronegative” threshold). Data presented in box plot and the line in the box indicate median. **P < .01, ***P < .001. Abbreviations: BBB, BNT162b2- BNT162b2- BNT162b2; BBM, BNT162b2-BNT162b2-mRNA-1273; IQR, interquartile range.
Figure 4.
Figure 4.
The neutralization activity of plasma samples against the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Plasma samples from participants who received a vaccine booster were collected prior to vaccination (day 0) and at day 28 after the booster vaccination and were screened for neutralizing activity against the Omicron variant of SARS-CoV-2. Plasma neutralizing activity comparison between participants who received the homologous (BBB) and heterologous (BBM) messenger RNA booster vaccine in the younger (aged <60 years, n = 28) and older (aged ≥60 years, n = 12) age groups. Box represents 25th and 75th percentile, line is median, with whiskers denoting extremes. Data analyzed using the Mann–Whitney U test. *P < .05. Abbreviations: BBB, BNT162b2- BNT162b2- BNT162b2; BBM, BNT162b2-BNT162b2-mRNA-1273; PRNT, plaque reduction neutralization test.
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