Potent, Persistent Cellular Immune Responses Elicited by Sequential Immunization of Rhesus Macaques with Ad5 Host Range Mutant Recombinants Encoding SIV Rev and SIV Nef

Patterson, L. Jean; Malkevitch, Nina; Zhao, Jun; Peng, Bo; Robert-Guroff, Marjorie
September 2002
DNA & Cell Biology;Sep2002, Vol. 21 Issue 9, p627
Academic Journal
Vaccines incorporating multiple HIV components should elicit broad immunity and protection against a spectrum of HIV strains. Early regulatory and accessory gene products are attractive candidates for such vaccines. Here, immunogenicity studies on SIV Rev and Nef expressed in replication competent Adenovirus type 5 host range mutant vectors (Ad5hr) are summarized. Interferon-γ (IFN-γ)-secreting cells in response to Env and Rev peptides were enumerated by ELISPOT after two sequential immunizations of 55 macaques with Ad5hr-SIVenv/rev. Responses to SIV Nef were assessed in 16 macaques also immunized with Ad5hr-SIVnef. Potent cellular immunity to both Rev and Nef was induced following the second Ad-recombinant immunization and persisted for at least 30 weeks. Persistent cellular immunity to SIV Env was also seen, with a mean of 700 IFN-γ-secreting cells per million PBMC. Rev and Env responses were positively correlated. While greater responses to early gene products occur in natural infection, as immunogens Rev and Nef elicited the same number of IFN-γ secreting cells as Env, after adjusting for differences in protein size. The same percentage of macaques also responded to Rev, Nef, and Env: 59, 63, and 64%, respectively. Overall, Ad5hrSIVenv/rev and -SIVnef were highly effective immunogens. Their contribution to protective efficacy will be addressed in future studies.


Related Articles

  • Isolation of a novel monkey adenovirus reveals a new phylogenetic clade in the evolutionary history of simian adenoviruses. de Motes, Carlos Maluquer; Hundesa, Ayalkibet; Almeida, Francisca C.; Bofill-Mas, Silvia; Girones, Rosina // Virology Journal;2011, Vol. 8 Issue 1, p125 

    Adenoviruses of primates include human (HAdV) and simian (SAdV) isolates classified into 8 species (Human Adenovirus A to G, and Simian Adenovirus A). In this study, a novel adenovirus was isolated from a colony of cynomolgus macaques (Macaca fascicularis) and subcultured in VERO cells. Its...

  • Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials. Shedlock, Devon J.; Silvestri, Guido; Weiner, David B. // Nature Reviews Immunology;Oct2009, Vol. 9 Issue 10, p717 

    Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficency viruses....

  • Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Hansen, Scott G.; Vieville, Cassandra; Whizin, Nathan; Coyne-Johnson, Lia; Siess, Don C.; Drummond, Derek D.; Legasse, Alfred W.; Axthelm, Michael K.; Oswald, Kelli; Trubey, Charles M.; Piatak, Michael; Lifson, Jeffrey D.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J. // Nature Medicine;Mar2009, Vol. 15 Issue 3, p293 

    The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion...

  • Animal Models Used for the Evaluation of Antiretroviral Therapies. P. Dias, Andreia S.; Bester, Megan J.; Britz, Rozane F.; Apostolides, Zeno // Current HIV Research;Oct2006, Vol. 4 Issue 4, p431 

    Several animal models for the study of HIV/AIDS have been established and characterized and have been widely used to study the pathogenesis of HIV/AIDS as well as vaccine development. The purpose of this study was to review the literature and identify the animal models most frequently used for...

  • Novel Simian Foamy Virus infection of wild Indian rhesus macaque (Macaca mulatta). Nandi, Jayashree S.; Chhangani, Anil K.; Mohnot, Surendra M. // Retrovirology;Jan2011 Supplement 1, Vol. 8, pA215 

    An abstract of the research paper titled,"Innate and adaptive anti-viral immune responses in MS patients treated with interferon-beta", is presented.

  • Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Raffatellu, Manuela; Santos, Renato L.; Verhoeven, David E.; George, Michael D.; Wilson, R. Paul; Winter, Sebastian E.; Godinez, Ivan; Sankaran, Sumathi; Paixao, Tatiane A.; Gordon, Melita A.; Kolls, Jay K.; Dandekar, Satya; Bäumler, Andreas J. // Nature Medicine;Apr2008, Vol. 14 Issue 4, p421 

    Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (TH17) cells in the ileal...

  • AIDS vaccine models: Challenging challenge viruses. Feinberg, Mark B.; Moore, John P. // Nature Medicine;Mar2002, Vol. 8 Issue 3, p207 

    Discusses AIDS vaccine models particularly rhesus macaque models. Experimental infection of rhesus monkeys with various simian immunodeficiency virus strains of differing virulence; Use of simian/human immunodeficiency viruses (SHIVs) as challenge viruses; Difference between SHIV-89.6P and...

  • Characterization of the Cutaneous Exanthem in Macaques Infected with a Nef Gene Variant of ... Sasseville, Vito G.; Rottman, James B.; Du, Zhenjian; Veazey, Ronald; Knight, Heather L.; Caunt, Diane; Desrosiers, Ronald C.; Lackner, Andrew A. // Journal of Investigative Dermatology;Jun98, Vol. 110 Issue 6, p894 

    The molecularly cloned viruses known as SIVmac239/R17Y and SIVmac239/YEnef cause extensive lymphocyte activation and induce an acute disease syndrome in macaque monkeys. One manifestation of this syndrome is a severe diffuse cutaneous maculopapular exanthem that is similar to the exanthem...

  • Cytotoxic T-Lymphocyte Escape Monitoring in Simian Immunodeficiency Virus Vaccine Challenge Studies. O'Connor, David H.; Allen, Todd M.; Watkins, David I. // DNA & Cell Biology;Sep2002, Vol. 21 Issue 9, p659 

    Several vaccine studies have ameliorated disease progression in simian–human immunodeficiency virus (SHIV) infections. The successes of these vaccines have been largely attributed to protective effects of cytotoxic T-lymphocyte (CTL) responses, although the precise correlates of immune...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics