Herman Ford Staats

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Professor of Pathology
Department / Division:
Pathology / Pathology Research
Address:
346m, Davison Building
Trent Drive
Durham, NC 27710
Office Telephone:
(919) 684-8823
Research Interests:

Areas of Research Interest:

Our laboratory studies methods to induce and regulate antigen-specific immune responses at the mucosal surfaces of the host. The mucosal tissues and surfaces are often the first site of contact with infectious agents, a common location of life-threatening cancers and 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

Adjuvants are substances commonly added to vaccines that enhance the induction of protective immune responses to the vaccine antigen. We have been successful at identifying substances with mucosal adjuvant activity such as the pro-inflammatory cytokine interleukin 1α/β (IL-1α/β). IL-1α/β provides effective nasal adjuvant activity in mice, rabbits and non-human primates. Recent studies performed in collaboration with Dr. Soman Abraham have determined that the chemical mast cell activator compound 48/80 provides effective nasal adjuvant activity in mice and rabbits. Our lab continues to search for compounds that provide safe and effective nasal adjuvant activity.

Recent studies in the lab have focused on the mechanism of action of IL-1α when used as a nasal vaccine adjuvant. IL-1α/β is a pro-inflammatory cytokine and we expected that its adjuvant mechanism of action was related to its ability to induce local production of pro-inflammatory cytokines that subsequently activated dendritic cells for enhanced antigen presentation activity. However, our studies determined that nasal IL-1α must directly activate CD11c+ dendritic cells for maximal adjuvant activity while IL-1α/β-induced cytokine responses (serum and nasal wash) were not required for maximal adjuvant activity after nasal delivery of IL-1α.

2. OPTIMIZING NASAL IMMUNIZATION FOR USE IN HUMANS

Nasal immunization studies in mice have demonstrated the ability of nasal immunization to induce protective immune responses equal to those induced by a vaccine delivered with a needle. However, when nasal immunization is performed in rabbits or non-human primates, animals with a nasal cavity structure/anatomy that closely resembles the human nasal cavity, nasal immunization is often not as effective as immunization delivered with a needle. Studies in our lab have demonstrated that an increased nasal residence time in rabbits correlates with increased vaccine immunogenicity. Studies are being performed to develop vaccine delivery techniques and vaccine formulations that maximize nasal residence time and therefore, the immunogenicity of the vaccine.

3. EVALUATING FACTORS THAT INFLUENCE THE INDUCTION OF FOOD ALLERGY AND DEVELOPING NOVEL MUCOSAL TREATMENTS FOR FOOD ALLERGY

The number of individuals with food allergy in steadily increasing in developed countries. The administration of food allergens via mucosal routes, a procedure known as “mucosal immunotherapy”, has provided encouraging results suggesting that mucosal immunotherapy is able to modify the host anti-food allergen response to reduce the severity of allergic responses. A new avenue of research in the laboratory is to 1) develop novel mucosal immunotherapy formulations (in collaboration with Dr. Wesley Burks, UNC Chapel Hill) and 2) evaluate the influence of environmental factors on the induction and severity of food allergies.

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