Herman Ford Staats, PhD

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Professor of Pathology
Associate Professor of Immunology
Associate Professor of Medicine
Department / Division:
Pathology / Pathology Research
Address:
346m, Davison Building
Trent Drive
Durham, NC 27710
Office Telephone:
(919) 684-8823
Training:
  • PhD, University of South Alabama, 1992
Fellowship:
  • Postdoctoral Fellow, Medicine, Duke University
Research Interests:
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:

1. IDENTIFYING AND CHARACTERIZING NOVEL MUCOSAL ADJUVANTS AND THEIR MECHANISM OF ACTION

2. OPTIMIZING NASAL IMMUNIZATION FOR USE IN HUMANS


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. More recent studies in our laboratory have focused on the use of cationic mast cell activators as vaccine adjuvants.

OPTIMIZE NASAL IMMUNIZATION IN NON-HUMAN PRIMATES
Nasal immunization in laboratory mice induces serum and mucosal antibody responses comparable to those induced by needle vaccination (i.e., intramuscular, subcutaneous). In rabbits and non-human primates, larger animal models that have a nasal cavity architecture similar to humans, nasal immunization is not as effective as parenteral immunization. Recent studies in our lab have determined that nasal immunization in rabbits or non-human primates often lacks efficacy due to inconsistencies in vaccine delivery to the nasal cavity of the host. For example, in one model using rabbits, a liquid vaccine formulation delivered intranasally inconsistently induced antigen-specific immune responses. Gamma scintigraphy imaging studies determined that the lack of vaccine efficacy was associated with rapid clearance of the vaccine formulation from the rabbit nasal cavity. Similar studies in non-human primates determined that a liquid vaccine formulation delivered intranasally was rapidly swallowed into the stomach. We are currently evaluating modified vaccine formulations and delivery techniques to determine if the immunogenicity of nasal vaccines can be increased if we enhance vaccine retention in the nasal cavity of rabbits or non-human primates.
Representative Publications:
  • Clapp, B; Golden, S; Maddaloni, M; Staats, HF; Pascual, DW. Adenovirus F protein as a delivery vehicle for botulinum B. BMC Immunology. 2010;11:36.  Abstract
  • Gwinn, WM; Kirwan, SM; Wang, SH; Ashcraft, KA; Sparks, NL; Doil, CR; Tlusty, TG; Casey, LS; Hollingshead, SK; Briles, DE; Dondero, RS; Hickey, AJ; Foster, WM; Staats, HF. Effective induction of protective systemic immunity with nasally administered vaccines adjuvanted with IL-1. Vaccine. 2010;28:6901-6914.  Abstract
  • Staats, HF; Kirwan, SM; Whisnant, CC; Stephenson, JL; Wagener, DK; Majumder, PP. Development of a bead immunoassay to measure Vi polysaccharide-specific serum IgG after vaccination with the Salmonella enterica serovar Typhi Vi polysaccharide. Clinical and Vaccine Immunology. 2010;17:412-419.  Abstract
  • Staats, HF; Leong, KW. Polymer hydrogels: Chaperoning vaccines. Nature Materials. 2010;9:537-538.  Abstract
  • Kunder, CA; St John, AL; Li, G; Leong, KW; Berwin, B; Staats, HF; Abraham, SN. Mast cell-derived particles deliver peripheral signals to remote lymph nodes. Journal of Experimental Medicine. 2009;206:2455-2467.  Abstract
  • McGowen, AL; Hale, LP; Shelburne, CP; Abraham, SN; Staats, HF. The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigen. Vaccine. 2009;27:3544-3552.  Abstract
  • Shelburne, CP; Nakano, H; St John, AL; Chan, C; McLachlan, JB; Gunn, MD; Staats, HF; Abraham, SN. Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues. Cell Host and Microbe. 2009;6:331-342.  Abstract
  • McLachlan, JB; Shelburne, CP; Hart, JP; Pizzo, SV; Goyal, R; Brooking-Dixon, R; Staats, HF; Abraham, SN. Mast cell activators: a new class of highly effective vaccine adjuvants. Nature Medicine. 2008;14:536-541.  Abstract
  • Thompson, JM; Nicholson, MG; Whitmore, AC; Zamora, M; West, A; Iwasaki, A; Staats, HF; Johnston, RE. Nonmucosal alphavirus vaccination stimulates a mucosal inductive environment in the peripheral draining lymph node. Journal of Immunology. 2008;181:574-585.  Abstract
  • Thompson, JM; Whitmore, AC; Staats, HF; Johnston, R. The contribution of type I interferon signaling to immunity induced by alphavirus replicon vaccines. Vaccine. 2008;26:4998-5003.  Abstract
  • Thompson, JM; Whitmore, AC; Staats, HF; Johnston, RE. Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen. Vaccine. 2008;26:4267-4275.  Abstract
  • Fujihashi, K; Staats, HF; Kozaki, S; Pascual, DW. Mucosal vaccine development for botulinum intoxication. Expert Review of Vaccines. 2007;6:35-45.  Abstract
  • Garmise, RJ; Staats, HF; Hickey, AJ. Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination. AAPS PharmSciTech. 2007;8:E81.  Abstract
  • Staats, HF; Alam, SM; Scearce, RM; Kirwan, SM; Zhang, JX; Gwinn, WM; Haynes, BF. In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity. Infection and Immunity. 2007;75:5443-5452.  Abstract
  • Maddaloni, M; Staats, HF; Mierzejewska, D; Hoyt, T; Robinson, A; Callis, G; Kozaki, S; Kiyono, H; McGhee, JR; Fujihashi, K; Pascual, DW. Mucosal vaccine targeting improves onset of mucosal and systemic immunity to botulinum neurotoxin A. Journal of Immunology. 2006;177:5524-5532.  Abstract
  • Nordone, SK; Peacock, JW; Kirwan, SM; Staats, HF. Capric acid and hydroxypropylmethylcellulose increase the immunogenicity of nasally administered peptide vaccines. AIDS Research and Human Retroviruses. 2006;22:558-568.  Abstract
  • Thompson, JM; Whitmore, AC; Konopka, JL; Collier, ML; Richmond, EM; Davis, NL; Staats, HF; Johnston, RE. Mucosal and systemic adjuvant activity of alphavirus replicon particles. Proceedings of the National Academy of Sciences of USA. 2006;103:3722-3727.  Abstract
  • Yu, JS; Peacock, JW; Vanleeuwen, S; Hsu, T; Jacobs, WR; Cayabyab, MJ; Letvin, NL; Frothingham, R; Staats, HF; Liao, HX; Haynes, BF. Generation of mucosal anti-human immunodeficiency virus type 1 T-cell responses by recombinant Mycobacterium smegmatis. Clinical and Vaccine Immunology. 2006;13:1204-1211.  Abstract
  • Haynes, BF; Fleming, J; St Clair, EW; Katinger, H; Stiegler, G; Kunert, R; Robinson, J; Scearce, RM; Plonk, K; Staats, HF; Ortel, TL; Liao, HX; Alam, SM. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science. 2005;308:1906-1908.  Abstract
  • Kobayashi, R; Kohda, T; Kataoka, K; Ihara, H; Kozaki, S; Pascual, DW; Staats, HF; Kiyono, H; McGhee, JR; Fujihashi, K. A novel neurotoxoid vaccine prevents mucosal botulism. Journal of Immunology. 2005;174:2190-2195.  Abstract
  • Egan, MA; Chong, SY; Hagen, M; Megati, S; Schadeck, EB; Piacente, P; Ma, BJ; Montefiori, DC; Haynes, BF; Israel, ZR; Eldridge, JH; Staats, HF. A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-specific humoral immune responses in cynomolgus macaques. Vaccine. 2004;22:3774-3788.  Abstract
  • Peacock, JW; Nordone, SK; Jackson, SS; Liao, HX; Letvin, NL; Yafal, AG; Gritz, L; Mazzara, GP; Haynes, BF; Staats, HF. Gender differences in human immunodeficiency virus type 1-specific CD8 responses in the reproductive tract and colon following nasal peptide priming and modified vaccinia virus Ankara boosting. Journal of Virology. 2004;78:13163-13172.  Abstract
  • Qimron, U; Paul, L; Bar-Haim, E; Bloushtain, N; Eisenbach, L; Staats, HF; Porgador, A. Non-replicating mucosal and systemic vaccines: quantitative and qualitative differences in the Ag-specific CD8(+) T cell population in different tissues. Vaccine. 2004;22:1390-1394.  Abstract
  • McLachlan, JB; Hart, JP; Pizzo, SV; Shelburne, CP; Staats, HF; Gunn, MD; Abraham, SN. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nature Immunology. 2003;4:1199-1205.  Abstract
  • Bradney, CP; Sempowski, GD; Liao, HX; Haynes, BF; Staats, HF. Cytokines as adjuvants for the induction of anti-human immunodeficiency virus peptide immunoglobulin G (IgG) and IgA antibodies in serum and mucosal secretions after nasal immunization. Journal of Virology. 2002;76:517-524.  Abstract
  • Staats, HF; Bradney, CP; Gwinn, WM; Jackson, SS; Sempowski, GD; Liao, HX; Letvin, NL; Haynes, BF. Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization. Journal of Immunology. 2001;167:5386-5394.  Abstract
  • Staats, HF; Ennis, FA. IL-1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens. Journal of Immunology. 1999;162:6141-6147.  Abstract
  • Porgador, A; Staats, HF; Itoh, Y; Kelsall, BL. Intranasal immunization with cytotoxic T-lymphocyte epitope peptide and mucosal adjuvant cholera toxin: selective augmentation of peptide-presenting dendritic cells in nasal mucosa-associated lymphoid tissue. Infection and Immunity. 1998;66:5876-5881.  Abstract
  • Porgador, A; Staats, HF; Faiola, B; Gilboa, E; Palker, TJ. Intranasal immunization with CTL epitope peptides from HIV-1 or ovalbumin and the mucosal adjuvant cholera toxin induces peptide-specific CTLs and protection against tumor development in vivo. Journal of Immunology. 1997;158:834-841.  Abstract
  • Staats, HF; Montgomery, SP; Palker, TJ. Intranasal immunization is superior to vaginal, gastric, or rectal immunization for the induction of systemic and mucosal anti-HIV antibody responses. AIDS Research and Human Retroviruses. 1997;13:945-952.  Abstract
  • Staats, HF; Nichols, WG; Palker, TJ. Mucosal immunity to HIV-1: systemic and vaginal antibody responses after intranasal immunization with the HIV-1 C4/V3 peptide T1SP10 MN(A). Journal of Immunology. 1996;157:462-472.  Abstract