Mucosal vaccines: the promise and the challenge (original) (raw)

• Levine, M. M. Immunization against bacterial diseases of the intestine. J. Pediatr. Gastroenterol. Nutr. 31, 336?355 (2000).
  CAS PubMed Google Scholar
• Lamm, M. E. Interactions of antigens and antibodies at mucosal surfaces. Annu. Rev. Microbiol. 51, 311?340 (1997).
  CAS PubMed Google Scholar
• Modlin, J. F. Poliomyelitis in the United States: the final chapter? JAMA 292, 1749?1751 (2004).
  CAS PubMed Google Scholar
• Kapikian, A. Z. et al. Efficacy of a quadrivalent rhesus rotavirus-based human rotavirus vaccine aimed at preventing severe rotavirus diarrhea in infants and young children. J. Infect. Dis. 174, S65?S72 (1996).
  PubMed Google Scholar
• Belshe, R. B. et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. N. Engl. J. Med. 338, 1405?1412 (1998).
  CAS PubMed Google Scholar
• Kozlowski, P. A. & Neutra, M. R. The role of mucosal immunity in prevention of HIV transmission. Curr. Mol. Med. 3, 217?228 (2003).
  CAS PubMed Google Scholar
• Belyakov, I. M. & Berzofsky, J. A. Immunobiology of mucosal HIV infection and the basis for development of a new generation of mucosal AIDS vaccines. Immunity 20, 247?253 (2004).
  CAS PubMed Google Scholar
• Neutra, M. R. & Kraehenbuhl J. P. in Mucosal Immunology 3rd edn (eds Ogra, P. L. et al.) 111?130 (Academic Press, San Diego, 2005).
  Google Scholar
• Brandtzaeg, P. et al. Regional specialization in the mucosal immune system: what happens in the microcompartments? Immunol. Today 20, 141?151 (1999).
  CAS PubMed Google Scholar
• van Egmond, M. et al. IgA and the IgA Fc receptor. Trends Immunol. 22, 205?211 (2001).
  CAS PubMed Google Scholar
• Kagnoff, M. F. & Eckmann, L. Epithelial cells as sensors for microbial infection. J. Clin. Invest. 100, S51?S55 (1997).
  CAS Google Scholar
• Izadpanah, A., Dwinell, M. B., Eckmann, L., Varki, N. M. & Kagnoff, M. F. Regulated MIP-3α/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am. J. Physiol. Gastroint. Liver Physiol. 280, G710?G719 (2001). One of a series of studies by this group, documenting the signals produced by epithelial cells in response to microorganisms and their products.
  CAS Google Scholar
• MacDonald, T. T. & Monteleone, G. Immunity, inflammation and allergy in the gut. Science 307, 1920?1925 (2005). A timely review of the basic cellular mechanisms underlying common gastrointestinal diseases that are associated with dysfunction of the mucosal immune system.
  CAS PubMed Google Scholar
• Rakoff-Nahoum, S., Pagliano, J., Esalmi-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118, 229?241 (2004). Recent evidence that TLR-mediated responses to non-pathogenic bacteria in the gut prevent local inflammation and are required for maintenance of a healthy epithelial barrier.
  CAS PubMed Google Scholar
• Backhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A. & Gordon, J. I. Host-bacterial mutualism in the human intestine. Science 307, 1915?1920 (2005). A fascinating overview of our long and intimate symbiotic relationship with commensal intestinal bacteria.
  PubMed Google Scholar
• Kozlowski, P. A., Cu-Uvin, S., Neutra, M. R. & Flanigan, T. P. Comparison of the oral, rectal, and vaginal immunization routes for induction of antibodies in rectal and genital tract secretions of women. Infect. Immun. 65, 1387?1394 (1997).
  CAS PubMed PubMed Central Google Scholar
• Kozlowski, P. A. et al. Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: influence of the menstrual cycle. J. Immunol. 169, 566?574 (2002). A detailed description of methods for analysis of antibodies in human secretions, and the influence of vaccination site on local antibody production.
  CAS PubMed Google Scholar
• Mestecky, J., Moro, I., Kerr, M. A. & Woof, J. M. in Mucosal Immunology, 3rd edn (eds Ogra, P. L. et al.) 153?182 (Academic Press, San Diego, 2005).
  Google Scholar
• Kaetzel, C. S., Robinson, J. K., Chintalacharuvu, K. R., Vaerman, J. P. & Lamm, M. The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. Proc. Natl Acad. Sci. USA 88, 8796?8800 (1991).
  CAS PubMed Google Scholar
• Hutchings, A. B., Helander, A., Silvey, K. J., Lucas, W. T. & Neutra, M. R. Secretory IgA antibodies against the σ1 outer capsid protein of reovirus type 1 Lang prevent infection of mouse Peyer's patches. J. Virol. 78, 947?957 (2004).
  CAS PubMed PubMed Central Google Scholar
• Robinson, J. K., Blanchard, T. G., Levine, A. D., Emancipator, S. N. & Lamm, M. E. A mucosal IgA-mediated excretory immune system in vivo. J. Immunol. 166, 3688?3692 (2001).
  CAS PubMed Google Scholar
• Black, K. P., Cummins, J. E. & Jackson, S. Serum and secretory IgA from HIV-infected individuals mediate antibody-dependent cellular cytotoxicity. Clin. Immunol. Immunopathol. 81, 182?190 (1996).
  CAS PubMed Google Scholar
• Eriksson, K. et al. Specific-antibody-secreting cells in the rectums and genital tracts of nonhuman primates following vaccination. Infect. Immun. 66, 5889?5896 (1998).
  CAS PubMed PubMed Central Google Scholar
• Kutteh, W. H., Mestecky, J. & Wira, C. R. in Mucosal Immunology, 3rd edn (eds Ogra, P. L. et al.) 1631?1646 (Academic Press, San Diego, 2005).
  Google Scholar
• Parr, E. L. & Parr, M. B. Immunoglobulin G is the main protective antibody in mouse vaginal secretions after vaginal immunization with attenuated herpes simplex virus type 2. J. Virol. 71, 8109?8115 (1997).
  CAS PubMed PubMed Central Google Scholar
• Kozlowski, P. A. et al. Modified wick method using Weck-Cel sponges for collection of human rectal secretions and analysis of mucosal HIV antibody. J. Acquir. Immune Defic. Syndr. 24, 297?309 (2000).
  CAS PubMed Google Scholar
• Yoshida, M. et al. Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity 20, 769?783 (2004).
  CAS PubMed Google Scholar
• Mantis, N. J. et al. Selective adherence of immunoglobulin A to murine Peyer's patch M Cells: evidence for a novel IgA receptor. J. Immunol. 169, 1844?1851 (2002).
  CAS PubMed Google Scholar
• Corthesy, B. et al. A pathogen-specific epitope inserted into recombinant secretory immunoglobulin is immunogenic by the oral route. J. Biol. Chem. 271, 33670?33677 (1996).
  CAS PubMed Google Scholar
• Belyakov, I. M. et al. The importance of local mucosal HIV-specific CD8+ cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12. J. Clin. Invest. 102, 2072?2081 (1998).
  CAS PubMed PubMed Central Google Scholar
• Veazey, R. S. & Lackner, A. A. Getting to the guts of HIV pathogenesis. J. Exp. Med. 200, 697?700 (2004). A review of the predilection of HIV and SIV for the intestinal mucosa and implications for pathogenesis and vaccines.
  CAS PubMed PubMed Central Google Scholar
• Brenchley, J. M. et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J. Exp. Med. 200, 749?759 (2004).
  CAS PubMed PubMed Central Google Scholar
• O'Leary, A. D. & Sweeney, E. C. Lymphoglandular complexes of the colon: structure and distribution. Histopathology 10, 267?283 (1986).
  CAS Google Scholar
• Neutra, M. R., Mantis, N. J. & Kraehenbuhl, J. -P. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nature Immunol. 2, 1004?1009 (2001).
  CAS Google Scholar
• Cook, D. N. et al. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12, 495?503 (2000).
  CAS Google Scholar
• Iwasaki, A. & Kelsall, B. L. Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3α, MIP-3β, and secondary lymphoid organ chemokine. J. Exp. Med. 191, 1381?1394 (2000). An excellent analysis of the DCs of Peyer's patches, and their functions in the specialized microcompartments within organized mucosal lymphoid tissues.
  CAS PubMed PubMed Central Google Scholar
• Zhao, X. et al. CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells. J. Immunol. 171, 2797?2803 (2003).
  CAS PubMed Google Scholar
• Hopkins, S. A., Niedergang, F., Corthesy-Theulaz, I. E. & Kraehenbuhl, J. P. A recombinant Salmonella typhimurium vaccine strain is taken up and survives within murine Peyer's patch dendritic cells. Cell. Microbiol. 2, 59?68 (2000).
  CAS PubMed Google Scholar
• Shreedhar, V. K., Kellsall, B. L. & Neutra, M. R. Cholera toxin induces migration of dendritic cells from the sub-epithelial dome region to T and B cell areas of Peyer's patches. Infect. Immun. 71, 504?509 (2003).
  CAS PubMed PubMed Central Google Scholar
• Iwasaki, A. & Kelsall, B. Unique functions of CD11b+, CD8α+, and double negative Peyer's patch dendritic cells. J. Immunol. 166, 4884?4890 (2001).
  CAS PubMed Google Scholar
• MacPherson, G. G. & Liu, L. M. Dendritic cells and Langerhans cells in the uptake of mucosal antigens. Curr. Top. Microbiol. Immunol. 236, 33?53 (1999).
  CAS PubMed Google Scholar
• Holt, P. G., Schon-Hegrad, M. A. & McMenamin, P. G. Dendritic cells in the respiratory tract. Int. Rev. Immunol. 6, 139?149 (1990).
  CAS PubMed Google Scholar
• Miller, C. J., McChesney, M. & Moore, P. F. Langerhans cells, macrophages and lymphocyte subsets in the cervix and vagina of rhesus macaques. Lab. Invest. 67, 628?634 (1992).
  CAS PubMed Google Scholar
• Niess, J. H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254?258 (2005). Identification of a novel mechanism for migration of DCs into the intestinal epithelium.
  CAS Google Scholar
• Fagarasan, S. & Honjo, T. Intestinal IgA synthesis: regulation of front-line body defences. Nature Rev. Immunol. 3, 63?72 (2003). Evidence for a mechanism whereby local IgA production can be rapidly increased during a mucosal memory response.
  CAS Google Scholar
• Mayer, L. & Shao L. Therapeutic potential of oral tolerance. Nature Rev. Immunol. 4, 407?419 (2004).
  CAS Google Scholar
• Belyakov, I. M., Hammond, S. A., Ahlers, J. D., Glenn, G. M. & Berzofsky, J. A. Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells. J. Clin. Invest. 113, 998?1007 (2004). Some nice detective work explaining how immunization through the skin can result in mucosal immune responses.
  CAS PubMed PubMed Central Google Scholar
• Kunkel, E. J. & Butcher, E. C. Plasma-cell homing. Nature Rev. Immunol. 3, 822?829 (2003).
  CAS Google Scholar
• Mora, J. R. et al. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424, 88?93 (2003).
  CAS PubMed Google Scholar
• Mestecky, J. The common mucosal immune system and current strategies for induction of immune responses in external secretions. J. Clin. Immunol. 7, 265?276 (1987).
  CAS PubMed Google Scholar
• Hieshima, K. et al. CC chemokine ligands 25 and 28 play essential roles in intestinal extravasation of IgA antibody-secreting cells. J. Immunol. 173, 3668?3675 (2004).
  CAS PubMed Google Scholar
• Lindholm, C., Naylor, A., Johansson, E. L. Quiding-Jarbrink, M. Mucosal vaccination increases endothelial expression of mucosal addressin cell adhesion molecule 1 in the human gastrointestinal tract. Infect. Immun. 72, 1004?1009 (2004).
  CAS PubMed PubMed Central Google Scholar
• Stagg, A. J., Kamm, M. A. & Knight, S. C. Intestinal dendritic cells increase T cell expression of α4β7 integrin. Eur. J. Immunol. 32, 1445?1454 (2002).
  CAS PubMed Google Scholar
• Haddad, W. et al. P-selectin and P-selectin glycoprotein ligand 1 are major determinants for TH1 cell recruitment to nonlymphoid effector sites in the intestinal lamina propria. J. Exp. Med. 198, 369?377 (2003).
  CAS PubMed PubMed Central Google Scholar
• Qimron, U. et al. Non-replicating mucosal and systemic vaccines: quantitative and qualitative differences in the Ag-specific CD8+ T cell population in different tissues. Vaccine 22, 1390?1394 (2004).
  CAS PubMed Google Scholar
• Staats, H. F., Montgomery, S. P. & Palker, T. J. Intranasal immunization is superior to vaginal, gastric, or rectal immunization for induction of systemic and mucosal anti-HIV antibody responses. AIDS Res. Hum. Retroviruses 13, 945?952 (1997).
  CAS PubMed Google Scholar
• Imaoka, K. et al. Nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces TH1/TH2 help for virus-specific immune responses in reproductive tissues. J. Immunol. 161, 5952?5958 (1998).
  CAS PubMed Google Scholar
• Rudin, A., Riise, G. & Holmgren, J. Antibody responses in the lower respiratory tract and male urogenital tract in humans after nasal and oral vaccination with cholera toxin B subunit. Infect. Immun. 67, 2884?2890 (1999).
  CAS PubMed PubMed Central Google Scholar
• Gallichan, W. S. & Rosenthal, K. L. Long-term immunity and protection against herpes simplex virus type 2 in the murine female genital tract after mucosal but not systemic immunization. J. Infect. Dis. 177, 1155?1161 (1998).
  CAS PubMed Google Scholar
• Egan, M. A. et al. Immunogenicity of attenuated vesicular stomatitis virus vectors expressing HIV type 1 Env and SIV Gag proteins: comparison of intranasal and intramuscular vaccination routes. AIDS Res. Hum. Retroviruses 20, 989?1004 (2004).
  CAS PubMed Google Scholar
• Enose, Y. et al. Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV. Virology 298, 306?316 (2002).
  CAS PubMed Google Scholar
• Belyakov, I. M. et al. Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge. Proc. Natl Acad. Sci. USA. 95, 1709?1714 (1998).
  CAS PubMed Google Scholar
• Ryan, E. J., Daly, L. M. & Mills, H. G. Immunoregulators and delivery systems for vaccination by mucosal routes. Trends Biotechnol. 19, 293?304 (2001). A review of mucosal adjuvants and strategies to increase the uptake of antigens into mucosal tissues.
  CAS PubMed Google Scholar
• Jones, B. D., Ghori, N. & Falkow, S. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. J. Exp. Med. 180, 15?23 (1994).
  CAS Google Scholar
• Sicinski, P. et al. Poliovirus type 1 enters the human host through intestinal M cells. Gastroenterology 98, 56?58 (1990).
  CAS PubMed Google Scholar
• Seong, S. Y., Cho, N. H., Kwon, I. C. & Jeong, S. Y. Protective immunity of microsphere-based mucosal vaccines against lethal intranasal challenge with Streptococcus pneumoniae. Infect. Immun. 67, 3587?3592 (1999).
  CAS PubMed PubMed Central Google Scholar
• Baca-Estrada, M. E., Foldvari, M., Babiuk, S. L. & Babiuk, L. A. Vaccine delivery: lipid-based delivery systems. J. Biotechnol. 83, 91?104 (2000).
  CAS PubMed Google Scholar
• Chabot, S. et al. A novel intranasal Protollin-based measles vaccine induces mucosal and systemic neutralizing antibody responses and cell-mediated immunity in mice. Vaccine 23, 1374?1383 (2005).
  CAS PubMed Google Scholar
• McNeela, E. A. et al. A mucosal vaccine against diptheria: formulation of crossreacting material (CRM97) of diptheria toxin with chitosan enhances local and systemic antibody and TH2 responses following nasal delivery. Vaccine 19, 1188?1198 (2000).
  CAS PubMed Google Scholar
• Frey, A. et al. Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting. J. Exp. Med. 184, 1045?1060 (1996).
  CAS PubMed Google Scholar
• Mantis, N. J., Frey, A. & Neutra, M. R. Accessibility of glycolipid and oligosaccharide epitopes on rabbit villus and follicle-associated epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 278, G915?G923 (2000).
  CAS PubMed Google Scholar
• Choi, W. S., Pal-Ghosh, R. & Morrow, C. D. Expression of human immunodeficiency virus type 1 (HIV-1) gag, pol, and env proteins from chimeric HIV-1-poliovirus minireplicons. J. Virol. 65, 2875?2883 (1991).
  CAS PubMed PubMed Central Google Scholar
• Tacket, C. O., Sztein, M. B., Losonsky, G. A., Wasserman, S. S. & Estes, M. K. Humoral, mucosal, and cellular responses to oral Norwalk virus-like particles in volunteers. Clin. Immunol. 108, 241?247 (2003).
  CAS PubMed Google Scholar
• Haneberg, B., Herland Berstad, A. K. & Holst, J. Bacteria-derived particles as adjuvants for non-replicating nasal vaccines. Adv. Drug Deliv. Rev. 51, 143?147 (2001).
  CAS PubMed Google Scholar
• Elson, C. O. & Dertzbaugh, M. T. Mucosal adjuvants. in Mucosal Immunology 3rd Edn. (eds Ogra, R. et al.) 967?986 (Academic Press, New York, 2005).
  Google Scholar
• van Ginkel, F. W., Jackson, R. J., Yuki, Y. & McGhee, J. R. The mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J. Immunol. 165, 4778?4782 (2000).
  CAS PubMed Google Scholar
• Mutsch, M. et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N. Engl. J. Med. 350, 896?903 (2004).
  CAS PubMed Google Scholar
• Lycke, N. From toxin to adjuvant: basic mechanisms for the control of mucosal IgA immunity and tolerance. Immunol. Lett. 97, 193?198 (2005). A review of the promise and problems of bacterial enterotoxins as mucosal adjuvants, and description of a new approach.
  CAS PubMed Google Scholar
• Belyakov, I. M., Ahlers, J. D., Clements, J. D., Strober, W. & Berzofsky, J. A. Interplay of cytokines and adjuvants in the regulation of mucosal and systemic HIV-specific CTL. J. Immunol. 165, 6454?6462 (2000).
  CAS PubMed Google Scholar
• Gallichan, W. S. et al. Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in the genital tract. J. Immunol. 166, 3451?3457 (2001).
  CAS PubMed Google Scholar
• McSorley, S. J., Ehst, B. D., Yu, Y. & Gewirtz, A. T. Bacterial flagellin is an effective adjuvant for CD4+ T cells in vivo. J. Immunol. 169, 3914?3919 (2002).
  CAS PubMed Google Scholar
• Malkevitch, N. & Robert-Guroff, M. A call for replicating vector prime-boost strategies in HIV vaccine design. Expert Rev. Vaccines 4, S105?S117 (2004). An extensive review of studies using live and non-living viral and bacterial vectors, and various systemic and mucosal vaccine strategies, to induce anti-HIV immune responses in monkeys.
  Google Scholar
• Lemiale, F. et al. Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system. J. Virol. 77, 10078?10087 (2003).
  CAS PubMed PubMed Central Google Scholar
• Milman, G. & Sharma, 0. Mechanisms of HIV/SIV mucosal transmission. AIDS Res. Hum. Retroviruses 10, 1305?1312 (1994).
  CAS PubMed Google Scholar
• Amerongen, H. M. et al. Transepithelial transport of HIV-1 by intestinal M cells: a mechanism for transmission of AIDS. J. Acquir. Immune Defic. Syndr. 4, 760?765 (1991).
  CAS PubMed Google Scholar
• Hu, J., Gardner, M. B. & Miller, C. J. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J. Virol. 74, 6087?6095 (2000).
  CAS PubMed PubMed Central Google Scholar
• Fujimura, Y. Evidence of M cells as portals of entry for antigens in the nasopharyngeal lymphoid tissue of humans. Virchows Arch. 436, 560?566 (2000).
  CAS PubMed Google Scholar
• Spira, A. I. et al. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J. Exp. Med. 183, 215?225 (1996).
  CAS PubMed Google Scholar
• Zhang, Z. -Q. et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286, 1353?1357 (1999).
  CAS PubMed Google Scholar
• Mazzoli, S. et al. HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals. Nature Med. 3, 1250?1257 (1997).
  CAS PubMed Google Scholar
• Kaul, R. et al. New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed, persistently seronegative Kenyan sex workers. Immunol. Lett. 79, 3?13 (2001).
  CAS PubMed Google Scholar
• Belyakov, I. M. et al. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nature Med. 7, 1320?1326 (2001).
  CAS PubMed Google Scholar
• Mäkitalo, B. et al. Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen. J. Gen. Virol. 85, 2407?2419 (2004).
  PubMed Google Scholar
• Bertley, F. M. N. et al. Control of simian/human immunodeficiency virus viremia and disease progression after IL-2-augmented DNA-modified vaccinia virus ankara nasal vaccination in nonhuman primates. J. Immunol. 172, 3745?3757 (2004).
  CAS PubMed Google Scholar
• Fuller, D. H. et al. Induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a DNA vaccine. J. Virol. 76, 3309?3317 (2002).
  CAS PubMed PubMed Central Google Scholar
• Nilsson, C. et al. Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm. AIDS 12, 2261?2270 (1998).
  CAS PubMed Google Scholar
• Tenner-Racz, K. et al. Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. Proc. Natl Acad. Sci. USA 101, 3017?3022 (2004).
  CAS PubMed Google Scholar
• Cromwell, M. A. et al. Induction of mucosal homing virus-specific CD8+T lymphocytes by attenuated simian immunodeficiency virus. J. Virol. 74, 8762?8766 (2000).
  CAS PubMed PubMed Central Google Scholar
• Crotty, S. et al. Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors. J. Virol. 75, 7435?7452 (2001). This paper reports the exploitation of a viral vector that naturally invades organized mucosal lymphoid tissues to deliver SIV genes and induce partial protection against subsequent mucosal challenge.
  CAS PubMed PubMed Central Google Scholar
• Burton, D. R. Antibodies, viruses, and vaccines. Nature Rev. Immunol. 2, 706?713 (2002). A thorough discussion of the potential importance of antibodies and their mechanisms of action in prevention and control of HIV.
  CAS Google Scholar
• Parren, P. W. H. I. et al. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J. Virol. 75, 8340?8347 (2001).
  CAS PubMed PubMed Central Google Scholar
• Veazey, R. S. et al. Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120. Nature Med. 9, 1?4 (2003).
  Google Scholar
• Fotopoulos, G. et al. Transepithelial transport of HIV-1 by M cells is receptor mediated. Proc. Natl Acad. Sci. USA 99, 9410?9414 (2002).
  CAS PubMed Google Scholar
• Janoff, E. N. & Smith, P. D. Emerging concepts in gastrointestinal aspects of HIV-1 pathogenesis and management. Gastroenterology 120, 607?621 (2001).
  CAS PubMed Google Scholar
• Fantini, J. et al. Synthetic and soluble analogues of galactosylceramide (GalCer) bind to the V3 domain of HIV-1 gp120 and inhibit HIV-1-induced fusion and entry. J. Biol. Chem. 272, 7245?7252 (1997).
  CAS PubMed Google Scholar
• Alfsen, A. & Bomsel, M. HIV-1 gp41 envelope residues 650?685 exposed on native virus act as a lectin to bind epithelial cell galactosyl ceramide. J. Biol. Chem. 277, 25649?25659 (2002).
  CAS PubMed Google Scholar
• Bomsel, M. Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nature Med. 3, 42?47 (1997).
  CAS PubMed Google Scholar
• Alfsen, A., Iniguez, P., Bouguyon, E. & Bomsel, M. Secretory IgA specific for a conserved epitope on gp41 envelope glycoprotein inhibits epithelial transcytosis of HIV-1. J. Immunol. 166, 6257?6265 (2001).
  CAS PubMed Google Scholar
• Hocini, H. et al. High-level ability of secretory IgA to block HIV type 1 transcytosis: contrasting secretory IgA and IgG responses to gp160. AIDS Res. Hum. Retroviruses 13, 1179?1185 (1997).
  CAS PubMed Google Scholar
• Matoba, N. et al. A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking antibodies. Proc. Natl Acad. Sci. USA 101, 13584?13589 (2004).
  CAS PubMed Google Scholar
• Clerici, M. et al. Serum IgA of HIV-exposed uninfected individuals inhibit HIV through recognition of a region within the α-helix of gp41. AIDS 16, 1731?1741 (2002).
  CAS PubMed Google Scholar
• Wright, P. F. et al. Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein. J. Infect. Dis. 189, 1221?1231 (2004).
  CAS PubMed Google Scholar
• McDermott, A. B. et al. Repeated low-dose mucosal simian immunodeficiency virus SIVmac239 challenge results in the same viral and immunological kinetics as high-dose challenge: a model for the evaluation of vaccine efficacy in nonhuman primates. J. Virol. 78, 3140?3144 (2004).
  CAS PubMed PubMed Central Google Scholar
• Wassén, L., Schön, K., Holmgren, J., Jertborn, M. & Lycke, N. Local intravaginal vaccination of the female genital tract. Scand. J. Immunol. 44, 408?414 (1996).
  PubMed Google Scholar
• Rudin, A., Johansson, E. -L., Bergquist, C. & Holmgren, J. Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans. Infect. Immun. 66, 3390?3396 (1998).
  CAS PubMed PubMed Central Google Scholar
• Quiding, M. et al. Intestinal immune responses in humans: oral cholera vaccination induces strong intestinal antibody responses and interferon-γ production and evokes immunological memory. J. Clin. Invest. 88, 143?148 (1991).
  CAS PubMed PubMed Central Google Scholar
• Kantele, A. et al. Differences in immune responses induced by oral and rectal immunizations with Salmonella typhi Ty21a: evidence for compartmentalization within the common mucosal immune system in humans. Infect. Immun. 66, 5630?5635 (1998).
  CAS PubMed PubMed Central Google Scholar
• Forrest, B. D., Shearman, D. J. C. & LaBrooy, J. T. Specific immune responses in humans following delivery of live typhoid vaccine. Vaccine 8, 209?212 (1990).
  CAS PubMed Google Scholar
• Ogra, P. L. & Karzon, D. T. Distribution of poliovirus antibody in serum, nasopharynx and alimentary tract following segmental immunization of lower alimentary tract with poliovaccine. J. Immunol. 102, 1423?1430 (1969).
  CAS PubMed Google Scholar
• Ogra, P. L. & Ogra, S. S. Local antibody response to poliovaccine in the human female genital tract. J. Immunol. 110, 1307?1311 (1973).
  CAS PubMed Google Scholar
• Kubota, M. et al. Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates. J. Immunol. 158, 5321?5329 (1997).
  CAS PubMed Google Scholar
• Vajdy, M. et al. Mucosal and systemic anti-HIV responses in rhesus macaques following combinations of intranasal and parenteral immunizations. AIDS Res. Hum. Retroviruses 20, 1269?1281 (2004).
  CAS PubMed Google Scholar
• Wang, S. -W. et al. Effective induction of simian immunodeficiency virus-specific systemic and mucosal immune responses in primates by vaccination with proviral DNA producing intact but noninfectious virions. J. Virol. 74, 10514?10522 (2000).
  CAS PubMed PubMed Central Google Scholar