Beyond immunogenicity - durability, dosing, and target populations for XBB.1.5 subunit COVID-19 boosters

Sep 29, 2026

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The correspondence evaluates Thuluva and colleagues’ phase 3 assessment of an updated XBB.1.5 RBD subunit COVID-19 vaccine, emphasizing superior immunogenicity to ancestral CORBEVAX™ and an overall reassuring safety profile in ages 5–80. Key concerns include insufficient follow-up to define durability, the trial’s exclusion of immunocompromised at-risk populations needing targeted subgroup evidence, limited policy guidance without head-to-head benchmarks, and practical challenges of a two-dose schedule versus single-dose strategies. It also notes strain-chasing constraints as variants evolve.

LanguageEnglish

CategoryHealthcare

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Pages1

Reading Time3 min

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Durability concerns

Follow-up duration and persistence of protection

At-risk populations

Immunocompromised inclusion and subgroup needs

Comparisons with updated boosters

Lack of direct head-to-head evidence

Dosing schedule practicality

Two-dose logistics vs single-dose strategy

Looking ahead

Strain-chasing limitations and conserved-epitope designs

Need for real-world effectiveness data

Correspondence Beyond immunogenicity: durability, dosing, and target populations for XBB.1.5 subunit COVID-19 boosters Jun Norkaew,a Chadaporn Nuchjunreed Gordon,b Schawanya Kaewpitoon Rattanapitoon,c and Nathkapach Kaewpitoon Rattanapitoonc,∗ aFaculty of Public Health, Vongchavalitkul University, Nakhon Ratchasima, Thailand bFaculty of Allied Health Sciences, Burapha University, Chonburi, Thailand cFMC Medical Center, Nakhon Ratchasima, Thailand We commend Thuluva and colleagues for their rigorous phase 3 evaluation of an updated XBB.1.5 RBD subunit COVID-19 vaccine in India.1 Their demonstration of superior immunogenicity versus the ancestral CORBEVAX™ plus a reassuring safety profile in individuals aged 5–80 years is especially relevant for LMICs where mRNA vaccine access remains limited. Several issues merit attention: 1. Durability: Follow-up (42 days for immunogenicity, 56 days for safety) is too short to assess persistence of protection. Waning antibody titres over months, as demonstrated in meta-analyses linking neutralising titres to variant protection, have guided booster timing policies globally.2 Longer-term follow-up is essential to determine the duration of effective protection. 2. At-risk populations: The trial excluded immunocompromised groups—who are prioritized for additional boosters by both WHO and CDC guidance.3 Their known attenuated response to vaccination necessitates targeted subgroup data to inform equitable vaccine strategies. 3. Comparisons with updated boosters: Without direct head-to-head comparison to contemporaneous mRNA or protein-based XBB.1.5 boosters, such asthe bivalent mRNA-1273.214 vaccine studied by Chalkias et al.,4 interpretation of relative advantage remains limited. Including such benchmarks would heighten policy relevance. 4. Dosing schedule practicality: The two-dose regimen may pose logistical challenges when many jurisdictions adopt single-dose booster strategies. Pragmatic evaluation of non-inferiority after a single dose in real-world settings is warranted. Looking ahead, although the study highlights the adaptability of yeast subunit platforms, the rapid shift from XBB.1.5 to JN.1—and emergent lineages like NB.1.8.1—exposes the constraints of a strain-chasing approach. Vaccine designs focussing on conserved epitopes or multivalent formulations may offer longerterm benefit.2 Parallel real-world effectiveness studies are required to verify whether strong immunogenicity translates into reductions in hospitalizations and mortality. In sum, the evidence from Thuluva et al. provides a practical basis for deploying updated subunit boosters in LMICs. Yet future work must focus on durability, inclusion of high-risk populations, dosing logistics, and anticipating viral evolution to sustain impact. Contributors All the authors have contributed equally in conceptualisation, writingoriginal draft, and writing-review and editing. Declaration of interests We declare no competing interests. References 1 Thuluva S, Paradkar V, Gunneri S, et al. Safety and immunogenicity of booster doses of an XBB.1.5 RBD subunit COVID-19 vaccine among individuals aged 5–80 years in India: a phase 3, single-blind, randomised controlled trial. Lancet Reg Health Southeast Asia. 2025;40:100642 . 2 Cromer D, Steain M, Reynaldi A, et al. Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe. 2022;3(1):e52– e61. [https://doi.org/10.1016/S2666-5247](https://doi.org/10.1016/S2666-5247)(21)00267-6. 3 WHO SAGE. Interim recommendations for an extended primary series with an additional vaccine dose for COVID-19 vaccination in immunocompromised persons. Interim guidance. [https://www](https://www). [who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_](who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_)[recommendation-immunocompromised-persons](recommendation-immunocompromised-perso

FAQs

Why is longer follow-up needed after the XBB.1.5 subunit booster trial?

The correspondence notes that the reported follow-up (42 days for immunogenicity, 56 days for safety) is too short to assess persistence of protection as antibody levels wane over months.

Which populations were excluded and why does that matter?

Immunocompromised groups were excluded, even though WHO and CDC guidance prioritize additional boosters for them; targeted subgroup data are considered necessary for equitable strategy decisions.

What comparison limitations affect interpretation for policy?

Without direct head-to-head comparison against contemporaneous mRNA or protein-based XBB.1.5 boosters, the correspondence argues that any relative advantage remains constrained.

Sep 29, 2026

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