Mammalian Meat Allergy and IgE to Alpha-gal in in Central Virginia: findings from a COVID-19 vaccine and patient cohort.

BACKGROUND: IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked with tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The "alpha-gal syndrome" (AGS) is recognized as being common in the southeastern USA, however prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. OBJECTIVE: Here we characterized the prevalence, as well as presentation and risk factors, of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regards to history of allergic disease. METHODS: Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. ImmunoCAP was used for IgE assays and ABO blood group was assessed by reverse typing using stored serum. Biobanked serum from COVID-19 patients was also investigated. RESULTS: Of 267 enrollees, median age was 42, 76% were female and 43 (16%) were sensitized to alpha-gal (cut-off 0.1 IU/mL), of which mammalian meat allergy was reported by 7 (2.6%). Sensitized subjects were i) older, ii) had higher total IgE levels but similar frequency of IgE to common respiratory allergens, and iii) were more likely to report tick bites than non-sensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat allergic than non-allergic subjects (GM 9.0 vs 0.5 IU/mL, P<0.001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. CONCLUSION: In central Virginia AGS is a dominant cause of adult food allergy with a prevalence approaching or exceeding 2%.

Tick bites, IgE to galactose-alpha-1,3-galactose and urticarial or anaphylactic reactions to mammalian meat: The alpha-gal syndrome.

The recent recognition of a syndrome of tick-acquired mammalian meat allergy has transformed the previously held view that mammalian meat is an uncommon allergen. The syndrome, mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Thus, fittingly, this allergic disorder is now called the alpha-gal syndrome (AGS). The syndrome is strikingly regional, reflecting the important role of tick bites in sensitization, and is more common in demographic groups at risk of tick exposure. Reactions in AGS are delayed, often by 2-6 h after ingestion of mammalian meat. In addition to classic allergic symptomatology such as urticaria and anaphylaxis, AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity and alpha-gal sensitization has also been linked with cardiovascular disease. The unusual link with tick bites may be explained by the fact that allergic cells and mediators are mobilized to the site of tick bites and play a role in resistance against ticks and tick-borne infections. IgE directed to alpha-gal is likely an incidental consequence of what is otherwise an adaptive immune strategy for host defense against endo- and ectoparasites, including ticks.

Alpha-Gal IgE Prevalence Patterns in the United States: An Investigation of 3,000 Military Recruits.

BACKGROUND: IgE to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) is an important cause of allergic reactions to mammalian meat. The "alpha-gal syndrome" is strongly associated with a preceding history of tick bites and in the United States is most commonly reported in parts of the southeast, but there has been limited investigation into national alpha-gal sensitization patterns and the relevance of other risk factors. OBJECTIVE: To systematically investigate alpha-gal IgE prevalence, regional patterns, and risk factors. METHODS: Alpha-gal IgE was measured by ImmunoCAP in biobanked serum samples collected from 3000 service members who presented for intake to 1 of 10 military bases in the central/eastern United States. Alpha-gal IgE sensitization (cutoff 0.1 international units/mL) was related to home of record at enlistment. RESULTS: Of the cohort, 2456 (81.9%) subjects were male, median age was 19 years (interquartile range: 18-22 years), and alpha-gal IgE was detected in 179 (6.0%). Home of record spanned all 50 states, with a median of 36 recruits per state (range: 3-261). The highest prevalence rates were in Arkansas (39%), Oklahoma (35%), and Missouri (29%), with several other southeastern states >10%. Granular mapping revealed sensitization patterns that closely mimicked county-level Amblyomma americanum reports and Ehrlichia chaffeensis infections. Sensitization was associated with male sex, rural residence, and White race in univariate and multivariable models. CONCLUSIONS: In this systematic survey, the prevalence of alpha-gal IgE among incoming military personnel was 6.0%. There were significant regional differences, with an overall pattern consistent with the known range of the lone star tick (A. americanum) and highest frequency in an area including Arkansas, Oklahoma, and Missouri.

Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273.

BACKGROUND: BNT162b2 (Pfizer/BioNTech, Comirnaty) and mRNA-1273 (Moderna, Spikevax) are messenger RNA (mRNA) vaccines that elicit antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) and have been approved by the US Food and Drug Administration to combat the coronavirus disease 2019 (COVID-19) pandemic. Because vaccine efficacy and antibody levels waned over time after the 2-shot primary series, the US Food and Drug Administration authorized a booster (third) dose for both mRNA vaccines to adults in the fall of 2021. OBJECTIVE: To evaluate the magnitude and durability of S-RBD immunoglobulin (Ig)G after the booster mRNA vaccine dose in comparison to the primary series. We also compared S-RBD IgG levels after BNT162b2 and mRNA-1273 boosters and explored effects of age and prior infection. METHODS: Surrounding receipt of the second and third homologous mRNA vaccine doses, adults in an employee-based cohort provided serum and completed questionnaires, including information about previous COVID-19 infection. The IgG to S-RBD was measured using an ImmunoCAP-based system. A subset of samples were assayed for IgG to SARS-CoV-2 nucleocapsid by commercial assay. RESULTS: There were 228 subjects who had samples collected between 7 and 150 days after their primary series vaccine and 117 subjects who had samples collected in the same time frame after their boost. Antibody levels from 7 to 31 days after the primary series and booster were similar, but S-RBD IgG was more durable over time after the boost, regardless of prior infection status. In addition, mRNA-1273 post-boost antibody levels exceeded BNT162b2 out to 5 months. CONCLUSION: The COVID-19 mRNA vaccine boosters increase antibody durability, suggesting enhanced long-term clinical protection from SARS-CoV-2 infection compared with the 2-shot regimen.

Trajectory of IgG to SARS-CoV-2 After Vaccination With BNT162b2 or mRNA-1273 in an Employee Cohort and Comparison With Natural Infection.

Three COVID-19 vaccines have received FDA-authorization and are in use in the United States, but there is limited head-to-head data on the durability of the immune response elicited by these vaccines. Using a quantitative assay we studied binding IgG antibodies elicited by BNT162b2, mRNA-1273 or Ad26.COV2.S in an employee cohort over a span out to 10 months. Age and sex were explored as response modifiers. Of 234 subjects in the vaccine cohort, 114 received BNT162b2, 114 received mRNA-1273 and six received Ad26.COV2.S. IgG levels measured between seven to 20 days after the second vaccination were similar in recipients of BNT162b2 and mRNA-127 and were ~50-fold higher than in recipients of Ad26.COV2.S. However, by day 21 and at later time points IgG levels elicited by BNT162b2 were lower than mRNA-1273. Accordingly, the IgG decay curve was steeper for BNT162b2 than mRNA-1273. Age was a significant modifier of IgG levels in recipients of BNT162b2, but not mRNA-1273. After six months, IgG levels elicited by BNT162b2, but not mRNA-1273, were lower than IgG levels in patients who had been hospitalized with COVID-19 six months earlier. Similar findings were observed when comparing vaccine-elicited antibodies with steady-state IgG targeting seasonal human coronaviruses. Differential IgG decay could contribute to differences observed in clinical protection over time between BNT162b2 and mRNA-1273.