Vaccination of Seronegative Volunteers with a Human Immunodeficiency Virus Type 1env/revDNA Vaccine Induces Antigen‐Specific Proliferation and Lymphocyte Production of β‐Chemokines

Abstract

There is a pressing need to test novel vaccine concepts in an effort to develop an effective vaccine for human immunodeficiency virus (HIV) type 1. A phase I clinical study was done to test the immunogenicity of an HIV env/rev DNA vaccine, which was administered intramuscularly to HIV-1-seronegative persons. Subjects received 3 doses of vaccine at a single concentration (100 or 300 microgram) at 0, 4, 8, and 24 weeks. In at least 1 of multiple assays, the 6 subjects who received the 300-microgram dose had DNA vaccine-induced antigen-specific lymphocyte proliferative responses and antigen-specific production of both interferon-gamma and beta-chemokine. Furthermore, 4 of 5 subjects in the 300 microgram-dose group responded to both the rev and env components of the vaccine. The responses did not persist within inoculated individuals and scored in different individuals at different times in the trial. This study supports that HIV-1 DNA vaccine antigens can stimulate multiple immune responses in vaccine-naive individuals, and it warrants additional studies designed to enhance DNA vaccine immunogenicity.

Induction of CD4+T cell-dependent CD8+type 1 responses in humans by a malaria DNA vaccine

“…4), we speculate that CD4 ϩ T cells function in a bystander helper capacity for CD8 ϩ T cell production of IFN-␥ following DNA vaccination. Consistent with this interpretation is our inability to detect Th2 (IL-4) responses or antibody responses following PfCSP DNA vaccination, and the failure by others to detect IL-4 responses in normal humans following immunization with an HIV-1 DNA vaccine (24).…”

“…Recently, the induction of antigen-specific lymphoproliferative, supernatant IFN-␥ and B-chemokine responses following Biojector i.m. administration of HIV env͞rev DNA in normal volunteers was reported (24). In that study, CTL were detected in only one assay and one of five volunteers tested, IFN-␥ was not detected by ELISPOT, IL-4 responses were not detected, and antibodies were not assessed.…”

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

“…Preclinical testing of DP6-001 demonstrated no significant adverse reactions in either rabbits or non-human primates despite the induction of robust immunity [2,3]. Previously tested HIV DNA vaccines have demonstrated excellent human safety profiles [4][5][6][7][8][9]. Recombinant protein-based HIV vaccines formulated with QS21 adjuvant have reported local reactions, but have shown limited systemic adverse events in humans [10][11][12][13][14][15].…”

Current prospects and future challenges for nasal vaccine delivery

“…41,42,43 Predominance of one set of cytokines over the other is generally indicative of polarization of Th responses, for example the presence of IL-4 and absence of IFN-g indicate a classical Th-2 polarized immune reaction 44 although these cytokines can also be released at the same time. 45,46,47 The varying cytokine profiles related to CTL and antibody production are fundamental in affording protection against a specific pathogen. Specific macrophage activation was found to play a crucial role in the eradication of Mycobacterium tuberculosis bacterial infections, 48 showing that the induction of specific immune responses may play a key role in determining whether a given vaccine product is effective.…”