Antibody Response of Heterologous vs Homologous mRNA Vaccine Boosters Against the SARS-CoV-2 Omicron Variant: Interim Results from the PRIBIVAC Study, A Randomized Clinical Trial

Abstract

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

Methods: This randomized, subject-blinded, controlled trial assess the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2+BNT162b2+BNT162b2; ‘BBB’) or heterologous mRNA booster vaccine (BNT162b2+BNT162b2+mRNA-1273; ‘BBM’). Primary endpoint was the level of neutralizing antibodies against SARS-CoV-2 wild-type and VOCs at Day 28.

Results: 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% CI, 18,210 to 27,517) vs BBM (29,751 IU/mL 95% CI, 25,281 to 35,011, p=0·034) as was the median level of neutralizing antibodies: BBB 99.0% (IQR 97·9 to 99·3%) vs BBM 99.3% (IQR 98·8 to 99·5%, p=0·021). On sub-group analysis, significant differences in mean spike antibody titer and live Omicron neutralization titer was only observed in older adults. Median surrogate neutralizing antibody level against all VOCs was also significantly higher with BBM in older adults, and against Omicron was BBB 72·8% (IQR 54·0 to 84·7%) vs BBM 84·3% (IQR 78·1 to 88·7%, p=0·0073). Both vaccines were well tolerated.
Conclusions: Heterologous mRNA-1273 booster vaccination induced a stronger neutralizing response against the Omicron variant in older individuals compared with homologous BNT123b2.

Note:
Funding Information: The study is supported in part by grants from Singapore National Medical Research Council [STPRG-FY19-001, COVID19RF-003, COVID19RF-011, COVID19RF-018, COVID19RF-060 and OFLCG19May-0034]. This live virus inhibition work was partially funded by the US Food and Drug Administration Medical Countermeasures Initiative contract (75F40120C00085). This work was also supported by the Medical Research Council [MR/W005611/1 to J.A.H.] G2P-UK: A national virology consortium to address phenotypic consequences of SARS-CoV- 2 genomic variation.

Conflict of Interests: Young reports personal fees from Astra-Zeneca, Gilead, Roche, Sanofi and Novacyte outside the submitted work. All other authors no potential conflicts of interest.

Ethical Approval: Written informed consent was obtained from all study participants. Ethical approval from National Healthcare Group Domain Specific Review Board (NHG DSRB, study reference 2021/00821).

Trial Registration: The study was registered with ClinicalTrials.gov (NCT05142319).

Keywords: COVID-19 vaccine booster, humoral immunity, omicron, live virus neutralization

JEL Classification: I18