Protection by Intranasal Immunization of a nef-Deleted, Nonpathogenic SHIV against Intravaginal Challenge with a Heterologous Pathogenic SHIV

Abstract

An effective vaccine against sexual transmission of human immunodeficiency virus (HIV) should elicit both systemic and mucosal immune responses. In this study, to examine the possibility of using an attenuated virus for mucosal immunization, four female macaques were intranasally or intravenously administered with a chimeric simian-human immunodeficiency virus with a deleted nef gene (SHIV-dn). Although all the monkeys had anti-HIV-1 antibodies with neutralizing activity in the plasma, the intranasally immunized monkeys had much higher levels of HIV-1 Env-specific IgG and IgA antibodies in mucosal secretions compared with the intravenously immunized monkeys. Moreover, three of four intranasally immunized monkeys were completely protected from intravaginal challenge with a pathogenic virus, SHIV-89.6P, whereas only one intravenously immunized monkey was protected. Thus, intranasal immunization of an attenuated virus can induce the protective efficacy against intravaginal infection.

Protective Efficacy of Nonpathogenic Nef‐Deleted SHIV Vaccination Combined with Recombinant IFN‐γ Administration against a Pathogenic SHIV Challenge in Rhesus Monkeys

“…Total RNAs were prepared from plasma with a QIAamp viral RNA kit (QIAGEN) according to the manufacturer's recommendations, and RT-PCR was performed using a Taqman RT-PCR kit (Perkin Elmer). RNAs of attenuated viruses and challenge virus were evaluated with primer pairs specific to SHIV NM-3rN and SHIV-C2/1, respectively, as previously described (14). These reactions were performed with a Prism 7700 Sequence Detector (Applied Biosystems, Foster City, Calif., U.S.A.) and analyzed using the manufacturer's software.…”

Murine Monoclonal Antibodies for Antigenic Discrimination of HIV-1 Envelope Proteins

“…Another noteworthy success was with attenuated SIV nef-deletion mutants (16) and with passive transfers of protective antibodies from SIV infected to naive animals (52). Similarly, SHIV infections have been shown to confer protection against heterologous challenges in animal models (17,46), and healthy HIV-1-infected humans have exhibited significant protective immunity against superinfections (12,43). Perhaps individuals once infected with immunodeficiency viruses are protected against heterologous challenges due to the natural evolution of viruses and respective immune responses within the patients (40,42,56).…”

Recent advances in the development of novel mucosal adjuvants and antigen delivery systems

“…Besides inducing strong mucosal immune responses, which parenteral immunization generally fails to do, mucosal immunization can also induce robust systemic immune responses. [2][3][4][5] Compared to parenteral routes, mucosal vaccine delivery offers other advantages such as lower costs, ease of administration, higher patient compliance, avoiding needle-stick injuries and sharps waste *Correspondence to: Wangxue Chen; Email: Wangxue.Chen@nrc-cnrc.gc.ca Submitted: 11/30/09; Revised: 02/09/10; Accepted: 02/17/10 Previously published online: www.landesbioscience.com/journals/vaccines/article/11561 DOI: 10.4161/hv.6.9.11561 disposal, 6,7 as well as higher capacity for mass immunizations such as during influenza pandemics. 8 Despite the obvious advantages of mucosal vaccines, few have made it to market, and fewer currently remain approved for use in humans.…”

“…1,3,6,[11][12][13][14] Most of these mucosal adjuvants and delivery systems have been extensively reviewed recently. [15][16][17][18][19][20] This review focuses on the recent approaches involving archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, 3',5'-cyclic diguanylic acid (c-di-GMP) and detoxified bacterial AB 5 toxins. M cell targeted mucosal vaccine delivery strategies are also discussed.…”