Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination.
Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile.
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA Oklahoma University Health Science Center, Department of Microbiology and Immunology, Oklahoma City, Oklahoma, USA.
Lori
L
Garman
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA.
Kenneth
K
Smith
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA.
Emily E
EE
Muns
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA.
Cathy A
CA
Velte
Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Christina E
CE
Spooner
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA.
Melissa E
ME
Munroe
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA Oklahoma University Health Science Center, Department of Microbiology and Immunology, Oklahoma City, Oklahoma, USA.
A Darise
AD
Farris
Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Michael R
MR
Nelson
Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Renata J M
RJ
Engler
Oklahoma Medical Research Foundation, Department of Arthritis and Clinical Immunology, Oklahoma City, Oklahoma, USA Oklahoma University Health Science Center, Department of Microbiology and Immunology, Oklahoma City, Oklahoma, USA Oklahoma University Health Science Center, Departments of Medicine and Pathology, Oklahoma City, Oklahoma, USA jamesj@omrf.org.
Judith A
JA
James
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D002097:C-Reactive Protein / Q000032:analysis*; D054357:Chemokine CXCL10 / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology*; D005006:Ethnicity; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C030325:anthrax toxin; D007073:Immunoglobulin E; D002097:C-Reactive Protein