Receiving an updated COVID-19 vaccine sparks a strong immune response against both previous strains and emerging variants, according to new research using a live SARS-CoV-2 virus.
The Oregon Health and Science University (OHSU)–led study suggested a clear benefit exists for updated vaccinations on a regular basis. That is especially the case in older adults or in those with underlying medical conditions, researchers wrote in their study that was published in Emerging Infectious Diseases.
“The virus is still circulating, it’s continuing to evolve, and it remains dangerous,” explained cosenior author Fikadu Tafesse, PhD, associate professor of molecular microbiology and immunology in the OHSU School of Medicine. “Sooner or later, there will be another variant that evades the immunity we have already built up. Our study demonstrates that it’s worthwhile to update our immune repertoire.”
The article published as a research letter noted, “Because novel SARS-CoV-2 variants continue to emerge, immunogenicity of XBB.1.5 monovalent vaccines against live clinical isolates needs to be evaluated. We report boosting of immunoglobulin G (IgG; 2.1×), immunoglobulin A (IgA; 1.5×), and total IgG/A/M (1.7×) targeting the spike receptor-binding domain and neutralizing titers against WA1 (2.2×), XBB.1.5 (7.4×), EG.5.1 (10.5×), and JN.1 (4.7×) variants.”
The authors pointed out that a monovalent COVID-19 vaccine containing the XBB.1.5 variant SARS-CoV-2 spike protein was approved in September 2023, but uptake has been low.
“Evaluating the immunogenicity of variant-adapted vaccines could incite trust in COVID-19 immunization, especially as neutralization-evading variants such as JN.1 emerge,” the researchers advised. “Studies have demonstrated induction of antibodies capable of neutralizing variant spike protein, but those studies used pseudo-typed viruses that recombinantly expressed variant spike proteins, not true SARS-CoV-2. We evaluated immunogenicity of XBB.1.5 vaccination in humans by using live SARS-CoV-2 clinical isolates to capture the biology of virus neutralization.”
OHSU healthcare workers were recruited in October 2023 and November 2023. The researchers collected paired serum samples from the 55 participants: one on the day the Moderna XBB.1.5 monovalent booster vaccine was administered and the other 21 days after vaccination. To identify recent infections, they used enzyme-linked immunosorbent to detect nucleocapsid antibodies.
The participants were 57% female with a mean age of 53 years. Preboost samples were identified in 20%, and postboost samples were positive for nucleocapsid antibodies in 27%.
“We included those samples to demonstrate generalized boosting in a population with heterogenous exposure history; however, removing those participants from analysis resulted in similar antibody induction by XBB.1.5 vaccination,” the researchers explained.
The results indicated that the XBB.1.5 vaccine “boosted total serum IgG/A/M targeting the spike RBD; postboost geometric mean titer (GMT) was 293 (95% CI; 195-442) versus preboost GMT of 174 (95% CI; 124-244), which represents a 1.7-fold change (P <.0001),” according to the report. “IgG isotypes demonstrated a greater increase than IgA isotypes (IgG postboost GMT 267 [95% CI; 196-363], preboost GMT 130 [95% CI; 95.7-176], a 2.1-fold change [P <.0001]; IgA postboost GMT 96.1 [95% CI; 74.6-124], preboost GMT 62.8 [95% CI; 50.3-78.3], a 1.5-fold change [P = .0002]).”
The researchers suggested that difference could be because of IM administration, which increases in IgG over IgA, adding, “IgM isotypes trended toward a slight increase, likely because IgM is short-lived; postboost GMT was 76.6 (95% CI; 57.6-102) versus preboost GMT 57.1 (95% CI; 44.5-73.2), a 1.3-fold change (P = .1548).”
The researchers added that the XBB.1.5 vaccine boosted neutralizing titers against the wild-type strain, with postboost GMT of 11,905 (95% CI; 8,454-16,766) versus preboost GMT 5,518 (95% CI; 3,899-7,809), a 2.1-fold change (P <.0001).
“The vaccine also boosted neutralizing titers against the vaccine-matched XBB.1.5 variant; postboost GMT was 838 (95% CI; 548-1,281) versus preboost GMT 114 (95% CI; 80.9-162), a 7.4-fold change (P <.0001). In addition, the vaccine boosted neutralizing titers against EG.5.1 by 10.5-fold (postboost GMT 824 [95% CI; 518-1,311] vs. preboost GMT 78.3 [95% CI; 55.0-112]; (P <.0001), and the JN.1 variant by 4.7-fold (postboost GMT 361 [95% CI; 270-483] vs. preboost GMT 77.6 [95% CI; 60.7-99.2]; P <.0001),” the authors advised.
The researchers concluded that their results “demonstrated that, before vaccination, persons have low ratios of antibodies capable of neutralizing XBB.1.5, EG.5.1, and JN.1, and that the XBB.1.5 monovalent vaccine increases the capacity of serum antibodies to neutralize contemporary variants. IgG, IgA, and total IgG/A/M titers were boosted, which likely includes expansion of a nonneutralizing compartment that mediates disease severity and longer-term protection through Fc effector functions.”
The study added that the XBB.1.5 monovalent vaccine was reported to reduce risk for COVID-19 hospitalization by 76.1% in Denmark, while in the United States, an analysis of two vaccine effectiveness data networks estimated 52% (95% CI; 47%-57%) and 43% (27%-56%) vaccine effectiveness against hospitalization.
“Overall, this work strongly supports use of the updated vaccine,” added cosenior author Marcel Curlin, MD, associate professor of medicine (infectious diseases) in the OHSU School of Medicine and medical director of OHSU Occupational Health. “In the big picture, COVID-19 is not going away but lining up alongside the other common respiratory illnesses such as flu and RSV, which cause relatively mild disease for most people and a lot of harm to a few.”
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