In vivo protective anti‐HIV immune responses in non‐human primates through DNA immunization

Abstract

An effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. In this context DNA immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides the opportunity to delete any genes of the infectious organism which code for antigens or pieces of antigens that may have deleterious effects. Our group has developed the use of nucleic acid immunization as a possible method of vaccination against Human immunodeficiency virus type 1 (HIV-1) [1,2,3,10,11,12]. Sera from non-human primates immunized with DNA vectors that express the envelope proteins from HIV-1 contain antibodies specific to the HIV-1 envelope. These sera also neutralize HIV-1 infection in vitro and inhibit cell to cell infection in tissue culture. Analysis of cellular responses is equally encouraging. T cell proliferation as well as cytotoxic T cell lysis of relevant env expressing target cells were observed. In addition, evidence that DNA vaccines are capable of inducing a protective response against live virus was demonstrated using a chimeric SIV/HIV (SHIV) challenge in vaccinated cynomologous macaques. We found that nucleic acid vaccination induced protection from challenge in one out of four immunized cynomolgus macaques and viral load was lower in the vaccinated group of animals versus the control group of animals. These data encouraged us to analyze this vaccination technique in chimpanzees, the most closely related animal species to man. We observed the induction of both cellular and humoral immune responses with a DNA vaccine in chimpanzees. These studies demonstrate the utility of this technology to induce relevant immune responses in primates which may ultimately lead to effective vaccines.

Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen

“…A combination of DNA priming followed by MVA or NYVAC boost induced higher CD8 ϩ T cell responses than any of the individual vaccines alone and resulted in protection against malaria. DNA-based HIV and SIV vaccines were shown to be immunogenic in chimpanzees (43,44) and rhesus macaques (45)(46)(47), but failed to protect the latter against a vigorous SIV mac251 challenge (46,47) or SIV ⌬b670 (45). DNA priming followed by MVA boost induced cell-mediated immune responses in nonhuman primates (26,45,48) and decreased viremia following exposure to a nonpathogenic SHIV-IIIB virus (44), pathogenic SHIV-89.6P (49), or HIV-1 (50).…”

Comparative Vaccine Studies in HLA-A2.1-Transgenic Mice Reveal a Clustered Organization of Epitopes Presented in Hepatitis C Virus Natural Infection

“…Numerous vaccines, and particularly vector-based candidates, can induce such responses, as demonstrated for a wide variety of antigens in various preclinical and clinical studies (4,7,24,40). Nonetheless, a systematic comparison of the vigor and scope of T-cell mediated responses induced by various vaccines expressing the same epitopes has been reported only in a limited number of studies (see, for example, references 18 and 32), most reports focus on a small number of antigens or epitopes encoded by the target pathogens.…”

M cell-targeted DNA vaccination

“…Such an alternative may lie with subunit vaccines or DNA vaccines, the latter being relatively easy to prepare and administer. Recent evidence shows that DNA vaccination can confer protective immunity against a number of infectious agents including influenza (4,5), herpes simplex virus (6), HIV (7,8), and Borrelia burgdorferi (9) infections. However, naked DNA immunizations have proven less than optimal for stimulating mucosal immunity (7,10,11) because they are administered peripherally as with conventional vaccines.…”