United States: It is metabolic well-being, with parameters that include blood pressure, blood sugar, and cholesterol, wherein these factors play a pivotal role in how immunizations against the virus of influenza work. There is evidence that the efficiency of the vaccination will be lower among those individuals with obesity than the ones who manage to keep their BMI within the normal range. However, researchers at St Jude Children’s Research Hospital have unearthed a crucial distinction: as it is not obesity in and of itself that decides the result, it is more towards the metabolic dysfunction that does.
As delineated in a study released today in Nature Microbiology, transitioning obese mice to a nutritious diet prior to influenza vaccination, as opposed to afterward, provided complete protection against a lethal flu dose, regardless of BMI.
“Our findings underscore that vaccines yield optimal results when administered to metabolically sound subjects,” articulated corresponding author Stacey Schultz-Cherry, PhD, hailing from the St. Jude Department of Host-Microbe Interactions and serving as co-director of the Center of Excellence for Influenza Research and Response. “Conversely, irrespective of outward appearances, metabolic impairment compromises vaccine efficacy.”
Previous investigations have elucidated that, even post-vaccination, 100% of obese mice succumbed to influenza virus exposure. Contrary to initial suppositions, restoring formerly obese mice to a healthy weight post-vaccination failed to improve outcomes. Even ostensibly healthy mice met the same fate upon viral exposure. Only preemptively adopting a nourishing diet four weeks ahead of vaccination engendered survival, yielding a profound impact despite elevated BMI.
“Our observation of this phenomenon was exhilarating, given the heightened susceptibility of obese mice to severe illness and fatality following infection,” Schultz-Cherry remarked. “Achieving 100% survival post-vaccination, where previously there was none, is indeed remarkable.” This enhanced survival rate suggests the researchers have unearthed a fundamental determinant of influenza vaccine efficacy.
Metabolic dysfunction undermines immune functionality
Amidst delving into how metabolic status influences responses to influenza vaccination, researchers discerned that poor metabolic health engenders immune dysfunction. T cells, pivotal players in antiviral defense, failed to mobilize in subjects harboring metabolic maladies at the time of vaccination, even upon subsequent viral exposure. Even when subjects transitioned to a healthful diet post-vaccination and maintained a normal BMI, the anti-influenza T cells remained inert in their dysfunctional state.
However, initiating a nutritious diet prior to vaccination bolstered T-cell efficacy, eliciting a robust antiviral response upon later exposure.
“The functional proficiency of T cells was markedly enhanced in metabolically sound subjects at the time of vaccination,” Schultz-Cherry elucidated. “It was not merely a matter of quantity or type; rather, it was their functional aptitude. Despite ample presence in the lungs, they remained inert. The transition to a healthful diet revived their functionality, albeit only if undertaken prior to vaccination.”
Anticipatory dietary modifications also assuaged inflammation. Pro-inflammatory cytokines are typically upregulated in obese subjects. Schultz-Cherry’s team observed a regression to a lower baseline cytokine level upon transitioning to a healthful diet before vaccination.
“A nourishing diet mitigated systemic meta-inflammation in these subjects, facilitating the restoration of epithelial innate immune responses,” Schultz-Cherry expounded. “We noted improved signaling of molecules such as interferons, notorious for dysregulation in obesity, thereby witnessing a restoration of immune functionality to its intended state.”
Enhancing metabolic health may augment influenza vaccine efficacy
“Our research underscores the primacy of metabolic health, as opposed to the phenotype of obesity, in determining vaccine efficacy,” Schultz-Cherry emphasized. “It is the metabolic status at the moment of vaccination that truly matters.”
While the study was confined to murine models, it heralds prospects for enhancing influenza vaccine efficacy in humans. The findings intimate that interventions aimed at ameliorating metabolic health may concurrently enhance subsequent influenza vaccinations. With the advent of metabolic modulating agents, particularly glucagon-like peptide 1 (GLP-1) agonists, a synergistic effect may be plausible.
“While definitive conclusions elude us, if the employment of GLP-1 drugs culminates in weight reduction and metabolic enhancement, we hypothesize a potential beneficial impact,” Schultz-Cherry conjectured. “Nonetheless, our paramount objective is to fortify protection for vulnerable demographics, and this study constitutes a stepping stone toward comprehending how.”