VaccineJan 1, 2026

Immune responses to different two-dose COVID-19 vaccines in long-term care and retirement home residents

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 2, 2026

Abstract

Bivalent vaccination induced cross-reactive antibody and T cell responses in older adults.

Higher immune responses were observed against ancestral SARS-CoV-2 than against Omicron-specific variants.
Omicron-specific neutralizing antibodies were enhanced after bivalent vaccination compared to monovalent vaccination.
Hybrid immunity contributed to increased humoral responses.
Neutralizing antibodies against Omicron BA.1 were boosted after the second bivalent vaccination, particularly in males.
Enhanced CD4T cell responses to the ancestral spike protein were noted after the second bivalent vaccine, especially in females.
Waning of anti-SARS-CoV-2 IgG occurred within 4 months after both bivalent vaccinations.

Simplified

BACKGROUND: Older adults were administered sequential heterogenous bivalent Ancestral/Omicron BA.1 and Ancestral/Omicron BA.4/5 SARS-CoV-2 mRNA vaccines in 2022-2023 in Ontario, Canada. Immunogenicity of this unique vaccination schedule was evaluated within the COVID in Long-Term Care Study, a multisite observational cohort of long-term care and retirement home residents.

METHODS: Humoral and cellular immunogenicity were evaluated 7-120 days after vaccinations with first bivalent (Ancestral/Omicron BA.1; BV1) and second bivalent (Ancestral/Omicron BA.4/5; BV2) vaccines. Hybrid immunity and biological sex were considered, with measurements of anti-spike and anti-RBD (receptor binding domain) IgG and IgA antibodies by ELISA, live SARS-CoV-2 ancestral and Omicron BA.1, BA.5 and XBB.1.5 neutralizing antibodies by microneutralization assays, and T cell responses to ancestral and Omicron BA.1, BA.4/5, and XBB.1.5 spike proteins by activation-induced marker assays.

RESULTS: Bivalent vaccination induced cross-reactive antibody and T cell responses. Higher responses were observed against ancestral SARS-CoV-2 than Omicron-specific variants, but Omicron-specific neutralizing antibodies were enhanced after bivalent vaccination compared to monovalent vaccination. Humoral responses were increased by hybrid immunity. Neutralizing antibodies against Omicron BA.1 were initially increased after BV2 compared to BV1 (especially in males), but in infection-naïve individuals there was back-boosting of ancestral neutralizing antibodies within 4 months. Enhanced CD4T cell responses to the ancestral spike protein were observed after BV2 compared to BV1 (particularly in females). Omicron BA.4/5 and XBB.1.5 neutralizing antibody and T cell responses were similar after BV2 and BV1. Waning of anti-SARS-CoV-2 IgG was observed after BV1 and BV2 within 4 months, and after BV1 but not BV2 for neutralizing antibodies and CD4T cell responses. + +

CONCLUSIONS: Humoral and cellular immune responses after two heterogenous bivalent vaccines were noninferior to those after a single bivalent vaccine within four months of vaccination. Continued surveillance of vaccine immunogenicity is essential to inform evidence-based decisions on vaccination of vulnerable older adults.

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Funding

Competing interests

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dawn M. E. Bowdish reports financial support was provided by Canadian Institutes of Health Research. Jessica A. Breznik reports financial support was provided by Global Nexus-Pfizer Postdoctoral Fellowship. Dawn M. E. Bowdish reports a relationship with AstraZeneca that includes: consulting or advisory. Dawn M. E. Bowdish reports a relationship with GSK that includes: consulting or advisory. Dawn M. E. Bowdish reports a relationship with Pfizer that includes: consulting or advisory. Matthew S. Miller reports a relationship with Bay Area Health Trust that includes: funding grants. Matthew S. Miller reports a relationship with JN Nova that includes: funding grants. Matthew S. Miller reports a relationship with Lactiga that includes: funding grants. Matthew S. Miller reports a relationship with Medicago that includes: funding grants. Matthew S. Miller reports a relationship with Providence Therapeutics that includes: funding grants. Matthew S. Miller reports a relationship with Boehringer Ingelheim that includes: speaking and lecture fees. Matthew S. Miller reports a relationship with Sanofi that includes: consulting or advisory and speaking and lecture fees. Matthew S. Miller reports a relationship with Seqirus that includes: consulting or advisory. Matthew S. Miller reports a relationship with Roche that includes: consulting or advisory. Matthew S. Miller reports a relationship with Grifols that includes: consulting or advisory. Matthew S. Miller reports a relationship with Aeroimmune Inc that includes: equity or stocks. Matthew S. Miller reports a relationship with Kapoose Creek Wellness that includes: equity or stocks. Matthew S. Miller reports a relationship with National Advisory Committee on Immunization that includes: board membership. Matthew S. Miller reports a relationship with Ontario Immunization Advisory Committee that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Immune responses to different two-dose COVID-19 vaccines in long-term care and retirement home residents

Abstract

Full Text

Funding

Competing interests

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