This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasaki, S. Articles by Okuda, K. Search for Related Content PubMed PubMed Citation Articles by Sasaki, S. Articles by Okuda, K.

 Previous Article  |  Next Article 

Infect. Immun., Sep 1997, 3520-3528, Vol 65, No. 9
Copyright © 1997, American Society for Microbiology

Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses to DNA vaccination against human immunodeficiency virus type 1

S Sasaki, T Tsuji, K Hamajima, J Fukushima, N Ishii, T Kaneko, KQ Xin, H Mohri, I Aoki, T Okubo, K Nishioka and K Okuda
Department of First Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.

To enhance immunity induced by DNA vaccination against human immunodeficiency virus type 1 (HIV-1), we evaluated the efficacy of monophosphoryl lipid A (MPL), an adjuvant of bacterial origin. BALB/c mice were intramuscularly injected with immunogenic DNA, encoding the env and rev genes of the HIV-1(IIIB) strain, formulated with MPL dissolved in different vehicles (MPL in stable emulsion and MPL in aqueous formulation). 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. 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. MPL also elicited stronger delayed-type hypersensitivity and cytotoxic-T- lymphocyte activity against HIV-1(IIIB) compared to DNA alone. HIV-1- specific IgG subclass analysis showed that MPL tends to facilitate IgG2a production, suggesting enhancement of a predominant T-helper-type- 1 response, and this enhancement may help to facilitate protective- antibody induction. Furthermore, a chloramphenicol acetyltransferase (CAT) assay was employed to determine whether MPL affected the gene expression process. Interestingly, both MPL preparations reduced CAT activity in the muscle injected with CAT expression vector but increased anti-CAT antibody production. These results indicate that MPL acts as an effective adjuvant for immunogenic DNA injection despite reduced expression of encoding protein in muscle. We conclude that MPL has a strong adjuvant effect on DNA vaccination against HIV-1.

This article has been cited by other articles:

• Wang, X., McGrath, S. C., Cotter, R. J., Raetz, C. R. H. (2006). Expression Cloning and Periplasmic Orientation of the Francisella novicida Lipid A 4'-Phosphatase LpxF. J. Biol. Chem. 281: 9321-9330 [Abstract] [Full Text]  
• Jin, Y., Cao, C., Li, P., Liu, X., Huang, W., Li, C., Ma, Q. (2005). Boosting Immune Response to Hepatitis B DNA Vaccine by Coadministration of Prothymosin {alpha}-Expressing Plasmid. CVI 12: 1364-1369 [Abstract] [Full Text]  
• Wang, X., Karbarz, M. J., McGrath, S. C., Cotter, R. J., Raetz, C. R. H. (2004). MsbA Transporter-dependent Lipid A 1-Dephosphorylation on the Periplasmic Surface of the Inner Membrane: TOPOGRAPHY OF FRANCISELLA NOVICIDA LpxE EXPRESSED IN ESCHERICHIA COLI. J. Biol. Chem. 279: 49470-49478 [Abstract] [Full Text]  
• Panilaitis, B., Johri, A., Blank, W., Kaplan, D., Fuhrman, J. (2002). Adjuvant Activity of Emulsan, a Secreted Lipopolysaccharide from Acinetobacter calcoaceticus. CVI 9: 1240-1247 [Abstract] [Full Text]  
• Childers, N. K., Miller, K. L., Tong, G., Llarena, J. C., Greenway, T., Ulrich, J. T., Michalek, S. M. (2000). Adjuvant Activity of Monophosphoryl Lipid A for Nasal and Oral Immunization with Soluble or Liposome-Associated Antigen. Infect. Immun. 68: 5509-5516 [Abstract] [Full Text]  
• Kusakabe, K.-i., Xin, K.-Q., Katoh, H., Sumino, K., Hagiwara, E., Kawamoto, S., Okuda, K., Miyagi, Y., Aoki, I., Nishioka, K., Klinman, D., Okuda, K. (2000). The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine. J. Immunol. 164: 3102-3111 [Abstract] [Full Text]  
• Singh, M., Briones, M., Ott, G., O'Hagan, D. (2000). Cationic microparticles: A potent delivery system for DNA vaccines. Proc. Natl. Acad. Sci. USA 97: 811-816 [Abstract] [Full Text]  
• Sasaki, S., Sumino, K., Hamajima, K., Fukushima, J., Ishii, N., Kawamoto, S., Mohri, H., Kensil, C. R., Okuda, K. (1998). Induction of Systemic and Mucosal Immune Responses to Human Immunodeficiency Virus Type 1 by a DNA Vaccine Formulated with QS-21 Saponin Adjuvant via Intramuscular and Intranasal Routes. J. Virol. 72: 4931-4939 [Abstract] [Full Text]  
• Sasaki, S., Hamajima, K., Fukushima, J., Ihata, A., Ishii, N., Gorai, I., Hirahara, F., Mohri, H., Okuda, K. (1998). Comparison of Intranasal and Intramuscular Immunization against Human Immunodeficiency Virus Type 1 with a DNA-Monophosphoryl Lipid A Adjuvant Vaccine. Infect. Immun. 66: 823-826 [Abstract] [Full Text]