Clinical Report: Comparing Booster Vaccine Strategies in Malaysia
Overview
This study evaluates longitudinal humoral immune responses following homologous and heterologous COVID-19 booster vaccination in Malaysia during the Omicron outbreak. The analysis focuses on anti-spike (anti-S) immunoglobulin G (IgG), anti-receptor-binding domain (anti-RBD) antibodies, and Omicron virus neutralization across 5 booster regimens.
Background
The emergence of the Omicron variant raised concerns about waning vaccine-induced immunity and reduced neutralizing activity. In Malaysia, both homologous and heterologous booster strategies were implemented after primary vaccination with mRNA, inactivated-virus, and viral-vector vaccines. Longitudinal data on antibody kinetics after these booster combinations remained limited in Malaysian and other Southeast Asian populations, prompting evaluation of humoral responses over time.
Data Highlights
Of 332 participants included in 24-week follow-up, 268 completed follow-up and 190 were included in the longitudinal immunogenicity analysis. Among those 190 participants, 52 received mR-mR, 32 received IV-IV, 26 received VV-VV, 49 received IV-mR, and 31 received VV-mR boosters.
Booster Regimen | Type |
|---|
mR-mR | Homologous |
IV-IV | Homologous |
VV-VV | Homologous |
IV-mR | Heterologous |
VV-mR | Heterologous |
Key Findings
The study included healthcare professionals and medical students from Manipal University College Malaysia and Universiti Malaya.
Five booster regimens were evaluated, including 3 homologous and 2 heterologous combinations.
Anti-S IgG and anti-RBD responses were assessed longitudinally, and Omicron neutralization was evaluated using a surrogate virus neutralization test.
Heterologous booster regimens, particularly IV-mR, produced higher and more sustained anti-S IgG and anti-RBD responses than the homologous IV-IV regimen.
At week 24, anti-S IgG and anti-RBD seropositivity remained 100% in the IV-mR group, compared with 15.63% and 18.75%, respectively, in the IV-IV group.
Omicron neutralization at week 24 was 95.92% with IV-mR, 83.87% with VV-mR, and 9.38% with IV-IV boosting.
Time to new SARS-CoV-2 infection differed significantly across the 5 vaccine groups.
Clinical Implications
The findings support the immunologic rationale for heterologous booster strategies incorporating an mRNA vaccine in individuals initially vaccinated with inactivated-virus or viral-vector vaccines. The IV-mR regimen was associated with particularly sustained antibody responses and Omicron neutralization over 24 weeks. The authors also caution that antibody dynamics alone cannot fully predict protection against emerging Omicron subvariants.
Conclusion
Heterologous booster vaccination, particularly IV-mR boosting, produced a superior longitudinal humoral immune response characterized by sustained anti-S IgG and anti-RBD antibodies and prolonged Omicron neutralization. These findings support mix-and-match booster approaches after inactivated-virus or viral-vector primary vaccination while underscoring the limits of antibody measurements alone as predictors of protection.
Related Resources & Content
Mixing versus matching booster vaccines: Longitudinal humoral immune kinetics against Omicron in a Malaysian cohort — Ashwathy Varadarajan Thundakattil, Rekha Prabhu, Girish Prabhu, Muthuvel Mani, Somsubhra De, Htoo Htoo Kyaw Soe, Charlotte Patrick Arjunan, Sumandeep Kaur Chahl, Debban A/L Ramesh, Ng Jian Chen, Soh Pei Qi, Jaayshree A/P Prakash, Nikhytha A/P Chandran, Mila Nu Nu Htay, Sabyasachi Das — International Journal of Infectious Diseases — 2026.
Emerging heterologous mRNA-based booster strategies within the COVID-19 vaccine landscape — Das R, Hyer RN, Burton P, Miller JM, Kuter BJ — Hum Vaccin Immunother — 2023.
Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain — Takano T, Sato T, Kotaki R, Moriyama S, Fukushi S, Shinoda M, et al — Nat Commun — 2023.
mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant — Garcia-Beltran WF, St Denis KJ, Hoelzemer A, Lam EC, Nitido AD, Sheehan ML, et al — Cell — 2022.
Homologous and heterologous Covid-19 booster vaccinations — Atmar RL, Lyke KE, Deming ME, Jackson LA, Branche AR, El Sahly HM, et al — N Engl J Med — 2022.
Real-world effectiveness of homologous and heterologous BNT162b2, CoronaVac, and AZD1222 booster vaccination against Delta and Omicron SARS-CoV-2 infection — Suah JL, Tng BH, Tok PSK, Husin M, Thevananthan T, Peariasamy KM, et al — Emerg Microbes Infect — 2022.
Heterologous versus homologous COVID-19 booster vaccinations for adults: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials — Asante MA, Michelsen ME, Balakumar MM, Kumburegama B, Sharifan A, Thomsen AR, et al — BMC Med — 2024.
