AIDSWEEKLY Plus, Monday, 15 September 1997
Daniel J. DeNoon, Senior Editor
An experimental naked DNA HIV vaccine elicited anti-HIV antibodies in vastly higher quantities and of superior quality when administered with monophosphoryl lipid A (MPL) adjuvant.
"MPL has a strong adjuvant effect on DNA vaccination against HIV-1," concluded Shin Sasaki of Yokohama City University School of Medicine and colleagues, who reported their findings in the journal Infection and Immunity ("Monophosphoryl Lipid A Enhances Both Humoral and Cell- Mediated Immune Responses to DNA Vaccination against Human Immunodeficiency Virus Type 1," Infect Immune, 1997;65(9):3250-8).
DNA vaccination is very efficient at eliciting cell- mediated immunity directed at encoded antigens. But it usually induces only low-level antibody responses.
As both types of immune responses are considered necessary for an HIV vaccine, most researchers in the field are working on combined vaccine regimens in which DNA vaccination is followed by boosting with a peptide subunit vaccine (the so- called prime/boost approach).
Sasaki et al. took a different approach, seeking to broaden the immunogenicity of a DNA vaccine by use of an adjuvant.
In their experiments, they used MPL (Ribi ImmunoChem), a preparation derived from the lipopolysaccharide (LPS) of Salmonella minnesota R595.
The researchers gave mice intramuscular injections with a DNA vaccine encoding the env and rev genes of the IIIB strain of HIV-1 either with or without MPL. Two MPL formulations were tested, one a stable emulsion and the other an aqueous solution.
"The sera from mice immunized with the two preparations of MPL revealed 2(6) to 2(9) times higher HIV-1-specific immunoglobulin G (IgG) titers than the sera from mice immunized without MPL," Sasaki et al. wrote. "In virus neutralization tests for HIV-1[IIIB] by p24 assay and antifusion assay of infected MOLT-4 cells, MPL tends to elicit antibody more protective than antibody elicited without adjuvant."
As demonstrated by delayed-type hypersensitivity tests and cytotoxic T-lymphocyte (CTL) activity, MPL also boosted cellular immune responses elicited by DNA vaccination. This effect appeared due to facilitation of IgG2a production, characteristic of a predominant T-helper type 1 immune response.
"Interestingly, both MPL preparations reduced CAT activity in the muscle injected with CAT expression vector but increased anti-CAT antibody production," Sasaki et al. noted. "These results indicate that MPL acts as an effective adjuvant for immunogenic DNA injection despite reduced expression of encoding protein in muscle."
The corresponding author for this study is Kenji Okuda, Department of Bacteriology, Yokohama City University School of Medicine, Yokohama 236, Japan.
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