Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909)

• Published in: Vaccine Vol. 32; no. 50; pp. 6847 - 6854
• Main Authors: Minang, Jacob T., Inglefield, Jon R., Harris, Andrea M., Lathey, Janet L., Alleva, David G., Sweeney, Diane L., Hopkins, Robert J., Lacy, Michael J., Bernton, Edward W.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 28.11.2014; Elsevier; Elsevier Limited
• Subjects: adjuvants; Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Anthrax; Anthrax - immunology; Anthrax - prevention & control; anthrax toxin; Anthrax Vaccines - administration & dosage; Anthrax Vaccines - immunology; antibodies; Antibodies, Bacterial - blood; Applied microbiology; Bacteriology; Biological and medical sciences; Biomarkers; BioThrax; blood serum; C-reactive protein; C-Reactive Protein - analysis; cell-mediated immunity; clinical trials; CPG 7909; cryopreservation; Cytokine; Cytokines - blood; Double-Blind Method; Drug dosages; Enzyme-Linked Immunospot Assay; Enzymes; Fundamental and applied biological sciences. Psychology; Haplotypes; Humans; humoral immunity; Immune system; Immunity, Innate; Immunization; immunoglobulin G; Immunoglobulin G - blood; Injections, Intramuscular; innate immunity; interferon-gamma; interleukin-6; Lymphocytes; Microbiology; Miscellaneous; Oligodeoxyribonucleotides - administration & dosage; Peptides; Proteins; T cell; T-lymphocytes; T-Lymphocytes - immunology; Vaccination - methods; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccine; BioThrax; Anthrax; T cell; CPG 7909; Cytokine; Bacillus anthracis; Immunization; Natural immunity; Cellular immunity; Bacillaceae; Infection; Bacillales; T-Lymphocyte; Bacteriosis; Bacteria; BioThrax(®)
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2014.01.096

•BioThrax® Plus CPG 7909 (0.25mg) in 2 vaccinations was sufficient to induce IFNγ+ cells.•IP-10 is a successful serum marker of CPG 7909 in vaccines delivered intramuscularly.•Absolute lymphocyte count was confirmed as a marker of CPG 7909 in this vaccine.•A pool of HLA class II PA-derived peptides were suitable T cell recall antigens.•CPG 7909 was confirmed to increase antigen-specific humoral immunity. NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax® (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24–48h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity.