Mucosal Immunity to SIV in Rhesus Macaques

Pauza, Charles David

Abstract

Genetically engineered bacterial strains were developed and used as live, oral vaccines to immunize against mucosal SIV infection in rhesus macaques. RESULTS We developed recombinant Salmonella typhimurium strains that express the SIV p27 antigen from a chromosomally-inserted expression construct. Live Salmonella were delivered by intragastric intubation of juvenile rhesus macaques and immune responses to the bacterial vector and the recombinant protein were characterized. In parallel animals received intramuscular immunization with purified, recombinant p27 antigen in polyphosphazene adjuvant. Intragastric immunization with recombinant bacteria elicited strong lymphoproliferative responses to Salmonella and to the viral protein without generating a measurable serum immunoglobulin response. Intramuscular immunization with soluble viral protein failed to elicit lymphoproliferative responses but generated high levels of serum antibody. Intragastric immunization did not boost the serum immunoglobulin response initiated by prior intramuscular immunization. Likewise, intramuscular boosting did not increase levels of lymphoproliferative responses to viral antigen. Immunized animals were challenged with a defined SHIV89.6PD inoculum and outcomes of challenge were assessed for information regarding viral immunity mechanisms. FUTURE DIRECTIONS Test the capacity for Salmonella strains to deliver DNA constructs to mucosal tissues. Develop additional bacterial strains expressing other viral antigens. Test combination vaccination strategies. KEY WORDS AIDS, vaccine, mucosal, recombinant bacteria, Salmonella typhimurium FUNDING NIH R01 AI36643 and RR00167 PUBLICATIONS Pauza, C.D., D. Horejsh, and M. Wallace. 1998. Mucosal transmission of virulent and avirulent lentiviruses in macaques. AIDS Res. Human Retrovir. 14:S83-87. [J] Steger, K.K., M. Dykhuizen, J. Mitchen, P. W. Hinds, B. L. Preuninger, M. Wallace, J. Thomson, Y. Lu, and C.D. Pauza. 1998. CD4+ T cell and CD20+ B cell changes that Predict Rapid Disease Progression after SHIV89.6PD Inoculation of Rhesus Macaques. J. Virol. 72:1600-1605. [J]

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Center for Research Resources (NCRR)
• Type: Primate Research Center Grants (P51)
• Project #: 5P51RR000167-41
• Application #: 6454349
• Project Start: 2001-05-01
• Project End: 2002-04-30
• Support Year: 41
• Fiscal Year: 2001

Institution

• Name: University of Wisconsin Madison
• DUNS #: 161202122
• City: Madison
• State: WI
• Country: United States
• Zip Code: 53715

Publications

Kang, HyunJun; Mesquitta, Walatta-Tseyon; Jung, Ho Sun et al. (2018) GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition. Stem Cell Reports 11:197-211

Rhoads, Timothy W; Burhans, Maggie S; Chen, Vincent B et al. (2018) Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys. Cell Metab 27:677-688.e5

Ellis-Connell, Amy L; Balgeman, Alexis J; Zarbock, Katie R et al. (2018) ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment. J Virol 92:

Park, Mi Ae; Jung, Ho Sun; Slukvin, Igor (2018) Genetic Engineering of Human Pluripotent Stem Cells Using PiggyBac Transposon System. Curr Protoc Stem Cell Biol 47:e63

Ellis, Amy; Balgeman, Alexis; Rodgers, Mark et al. (2017) Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques. Infect Immun 85:

Rodrigues, Michelle A (2017) Female Spider Monkeys (Ateles geoffroyi) Cope with Anthropogenic Disturbance Through Fission-Fusion Dynamics. Int J Primatol 38:838-855

Buechler, Connor R; Bailey, Adam L; Lauck, Michael et al. (2017) Genome Sequence of a Novel Kunsagivirus (Picornaviridae: Kunsagivirus) from a Wild Baboon (Papio cynocephalus). Genome Announc 5:

Wu, Hong; Whritenour, Jessica; Sanford, Jonathan C et al. (2017) Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity Reactions in Cynomolgus Monkeys. Toxicol Pathol 45:127-133

Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732

Kalin, Ned H (2017) Mechanisms underlying the early risk to develop anxiety and depression: A translational approach. Eur Neuropsychopharmacol 27:543-553