Retinoic acid as a vaccine adjuvant enhances CD8 + T cell response and mucosal protection from viral challenge

Xuefang Tan, Jamie L. Sande, Jeffrey S. Pufnock, Joseph Blattman, Philip D. Greenberg

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Vaccine-induced memory T cells localized at mucosal sites can provide rapid protection from viral infection. All-trans-retinoic acid (ATRA) has been shown to act physiologically to induce the expression of gut-homing receptors on lymphocytes. We tested whether the administration of exogenous ATRA during a systemic vaccination of mice could enhance the generation of mucosal CD8 + T cell immunity, which might represent a strategy for establishing better protection from viral infection via mucosal routes. ATRA induced the expression of CCR9 and α4β7 on both mouse and human CD8 + T cells activated in vitro. The administration of ATRA to mice during in vivo priming with a replication-defective recombinant adenovirus vector expressing the lymphocytic choriomeningitis virus glycoprotein (LCMVgp) (Ad5gp) increased numbers of both effector and memory T cells in intestinal mucosal tissues and showed higher frequencies of systemic central memory-like T cells that exhibited enhanced proliferation during boosting immunization with recombinant modified vaccinia virus Ankara expressing LCMVgp (MVAgp). Mice that received ATRA during Ad5gp vaccination were more resistant to intravaginal challenge by recombinant vaccinia virus expressing LCMVgp (VVgp), reflecting in part stronger T cell recall responses in situ. Thus, ATRA appears to be useful as an adjuvant during vaccination to increase memory T cell responses and protection from viral infection at mucosal sites and may facilitate the development of more effective vaccines against mucosally transmitted pathogens such as HIV.

Original languageEnglish (US)
Pages (from-to)8316-8327
Number of pages12
JournalJournal of Virology
Volume85
Issue number16
DOIs
StatePublished - Aug 2011
Externally publishedYes

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vaccine adjuvants
retinoic acid
Tretinoin
Vaccines
T-lymphocytes
T-Lymphocytes
Lymphocytic choriomeningitis virus
Virus Diseases
glycoproteins
Glycoproteins
Vaccinia virus
Vaccination
vaccination
mice
Lymphocyte Homing Receptors
infection
vaccines
Cytoprotection
Adenoviridae
adjuvants

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Retinoic acid as a vaccine adjuvant enhances CD8 + T cell response and mucosal protection from viral challenge. / Tan, Xuefang; Sande, Jamie L.; Pufnock, Jeffrey S.; Blattman, Joseph; Greenberg, Philip D.

In: Journal of Virology, Vol. 85, No. 16, 08.2011, p. 8316-8327.

Research output: Contribution to journalArticle

Tan, Xuefang ; Sande, Jamie L. ; Pufnock, Jeffrey S. ; Blattman, Joseph ; Greenberg, Philip D. / Retinoic acid as a vaccine adjuvant enhances CD8 + T cell response and mucosal protection from viral challenge. In: Journal of Virology. 2011 ; Vol. 85, No. 16. pp. 8316-8327.
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