Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients

Richard B Kennedy, Gregory A. Poland, Inna G. Ovsyannikova, Ann L Oberg, Yan Asmann, Diane E. Grill, Robert A. Vierkant, Robert M. Jacobson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically defined by the appearance of a lesion or "take" at the vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax® or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the smallpox vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated smallpox vaccines and/or effective antiviral therapy targets against poxvirus infections.

Original languageEnglish (US)
JournalVaccine
DOIs
StateAccepted/In press - Dec 21 2015

Fingerprint

Smallpox Vaccine
Humoral Immunity
Innate Immunity
humoral immunity
Cellular Immunity
cell-mediated immunity
vaccines
Antiviral Agents
Vaccines
Cicatrix
Poxviridae Infections
Orthopoxvirus
Attenuated Vaccines
Poxviridae
immune response
Smallpox
Vaccinia virus
lesions (plant)
Neutralizing Antibodies
vaccine development

Keywords

  • Antibodies
  • Antibody formation
  • Cellular immunity, Humoral
  • Immunity
  • Smallpox
  • Smallpox vaccine
  • Vaccinia virus

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients. / Kennedy, Richard B; Poland, Gregory A.; Ovsyannikova, Inna G.; Oberg, Ann L; Asmann, Yan; Grill, Diane E.; Vierkant, Robert A.; Jacobson, Robert M.

In: Vaccine, 21.12.2015.

Research output: Contribution to journalArticle

Kennedy, Richard B ; Poland, Gregory A. ; Ovsyannikova, Inna G. ; Oberg, Ann L ; Asmann, Yan ; Grill, Diane E. ; Vierkant, Robert A. ; Jacobson, Robert M. / Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients. In: Vaccine. 2015.
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