Since the mucosal tissues and surfaces are: 1)
often
the first site of contact with infectious agents,
2) the most common location of life-threatening
cancers and 3) in constant contact
with environmental antigens, a better understanding
of factors that control the induction and regulation
of mucosal immune responses may aid the development
of vaccines and treatments for infectious agents
such as HIV and agents of bioterrorism, cancers and
environmental allergies. Research
interests in the Staats’ lab currently
focus
on:
- IDENTIFYING AND CHARACTERIZING
NOVEL MUCOSAL ADJUVANTS AND THEIR MECHANISM OF
ACTION
- DEFINING
THE MECHANISMS THAT CONTROL THE SPECIFICITY OF
VACCINE-INDUCED SERUM IgG AND MUCOSAL
IgA
- OPTIMIZING
NASAL IMMUNIZATION IN NON-HUMAN
PRIMATES
IDENTIFYING AND CHARACTERIZING NOVEL MUCOSAL ADJUVANTS AND THEIR MECHANISM
OF ACTION
We have been successful at identifying novel mucosal adjuvants. However,
their cellular and molecular mechanism of mucosal adjuvanticity remains to be
determined. We have determined that the combination of IL-1α, IL-12
and GM-CSF used as a mucosal adjuvant enhanced the expression of the costimulatory
molecule B7.1 and the antigen-presenting molecule MHC Class II on antigen-presenting
cells within the nasal-associated lymphoid tissue (NALT). Increased expression
of B7.1 and MHC Class II correlated with the induction of antigen-specific immunity
after nasal immunization. Our previous work suggests that dendritic cells
(DC) are the predominant antigen-presenting cell (APC) responsible for the induction
of vaccine-induced immune responses after nasal immunization. However,
it is not clear if the mucosal adjuvants directly or indirectly activate the
NALT DC. We are currently investigating if nasal vaccine adjuvants mediate
their adjuvant activity by activating mucosal epithelial cells that then activate
APC or if nasal vaccine adjuvants directly activate APC. A
better understanding of the cellular and molecular mechanisms
associated with the activity of nasally administered adjuvants
will guide the development of more effective nasal adjuvants
and vaccines.
DEFINING THE MECHANISMS THAT CONTROL THE SPECIFICITY OF VACCINE-INDUCED SERUM
IgG AND MUCOSAL IgA
Studies
performed in Dr. Staats laboratory indicate that antigen-specific
IgG and IgA recognize distinct linear epitopes within
HIV-1 glycoprotein 41. Dr.
Staats lab is currently funded to evaluate how the route of immunization, adjuvant
and form of antigen (recombinant protein, infectious virus) affect the specificity
of antigen-specific serum IgG and mucosal IgA. A
better understanding
of the factors that contribute to and regulate the induction
of antigen-specific antibody, IgG and IgA, may provide
important information that will assist the development
of vaccines designed to induce epitope-specific immune
responses.
OPTIMIZE NASAL IMMUNIZATION IN NON-HUMAN PRIMATES
Our
preliminary data
indicates that nasal immunization of non-human primates
using IL-1α and GM-CSF as adjuvant induced antigen-specific humoral immunity
in both the systemic and mucosal compartments. However, the magnitude of
the response was not optimal and there was significant animal-animal variation. Additional
studies are required to determine antigen doses, adjuvant doses, and the frequency
of immunization that induces maximal antigen-specific systemic and mucosal IgG
and IgA. Optimization of nasal immunization in non-human
primates will allow studies to be performed to evaluate
the contribution of vaccine-induced,
antigen-specific mucosal IgA in protection against infectious
agents such as HIV, anthrax spores and monkey pox (as
a model for smallpox).
