Comparison of intranasal and intramuscular immunization against human immunodeficiency virus type 1 with a DNA-monophosphoryl lipid A adjuvant vaccine

Abstract

We compared immune responses to intranasal and intramuscular DNA vaccinations against human immunodeficiency virus type 1 with monophosphoryl lipid A (MPL) used as an adjuvant. Both routes of vaccination resulted in similar levels of cell-mediated immunity, but the intestinal secretory immunoglobulin A response was higher following intranasal immunization than after intramuscular immunization. MPL demonstrated its adjuvanticity in vaccination by both routes.

FIG. 1

Humoral immune responses induced by MPL adjuvant-DNA vaccination through the i.m. (A) and i.n. (B) routes. Mice were immunized once with 4 μg of IIIB/REV formulated with the indicated doses of MPL-SE. HIV-1 principal neutralizing determinant-specific titers of serum IgG, IgG1, and IgG2a and fecal sIgA were measured by ELISA using sera collected 4 weeks after immunization. The results are expressed as the mean ± standard error of the mean of five (experimental group) or four (control group) mice. The symbols * and + indicate a significantly enhanced antibody response compared with either the response obtained with IIIB/REV alone delivered via the same route or the response of the group administered vaccine plus adjuvant i.m., respectively (P < 0.05). Similar results were obtained in another experiment. No antibody was detected in the group administered empty vector (pCMV-empty) and 20 μl of MPL-SE via the i.n. route.

FIG. 2

Antigen-specific cytolytic activity of bulk splenic mononuclear cells harvested from mice immunized with MPL adjuvant-DNA vaccine administered via the i.m. (A) or i.n. (B) route. Splenocytes were harvested and cultured for 5 days with V3 peptide (also known as a CTL epitope of HIV-1 strain IIIB). Syngeneic cells (P815 cells) pulsed with or without the same peptide were used as targets, and the percent target cell lysis was determined by means of a 5-h ⁵¹Cr release assay. The activity was titrated with effector/target (E/T) cell ratios of 5, 20, and 80. Nonspecific cytolytic activity (not pulsed) was measured at an E/T ratio of 80. The results were obtained in duplicate assays and are expressed as the mean ± standard error of the mean of the four to five mice in each group. The symbol * indicates a significantly enhanced cytolytic response compared with the response of mice which received IIIB/REV alone via the same immunization route.