Original research

Generating neutralizing antibodies, Th1 response and MHC non restricted immunogenicity of HIV-I env and gag peptides in liposomes and ISCOMs with in-built adjuvanticity

Lokesh Agrawal¹ , W Haq² , Carl Veith Hanson³ and D Nageswara Rao⁴

¹Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana-46202, USA

²Department of Biopolymers, CDRI, Lucknow, India

³California Department of Health Services, Viral and Rickettsial Disease Laboratory, 850 Marina Bay Parkway, Richmond, CA 94804, USA

⁴Department of Biochemistry, AIIMS, New Delhi-110 029, India

author email corresponding author email

Journal of Immune Based Therapies and Vaccines 2003, 1:5doi:10.1186/1476-8518-1-5

Published:	25 November 2003

Abstract

For enhancing immunogenicity and develop vaccine strategies using peptide based constructs against HIV-1, a chimeric peptide containing V3 loop and transmembrane sequence of gp41 with two glycine motifs as spacer was constructed. The V3-gp41, gp41 peptide and p17 and p24 peptides separately or in a cocktail were entrapped with or without MA729 as an immunoadjuvant in liposomes or ISCOMs. The immunogenicity, antigen induced T-cell proliferation and cytokine profiles of various formulations were studied in four different inbred strains of mice of H-2^d, H-2^b, H-2^k and H-2^q haplotypes, keeping alum as a control adjuvant. Both liposomes and ISCOM preparations elicited high titer and long lasting antibody response (60 days and above). When compared to the alum formulation, the liposomes co-entrapped with MA729 produced high antibody levels, comparable with that induced by ISCOMs. Peptide in alum, liposomes and ISCOMs enhanced both antigen specific IgG2a and IgG2b isotypes and high T-cell stimulation index. Peptide formulations also induced antibodies with high affinity and in vitro neutralizated the formation of HIV-1 syncytia. T-cell supernatants contained high levels of IFN-γ and IL-2. Thus formulation in these adjuvants induced a predominant Th1 like response with MA729 as a versatile novel delivery vehicle for stimulating the appropriate arm of the immune response that can selectively modulate MHC class I or MHC class II response. The above peptide can be of wide vaccination interest as a means to improve immune responses to several other HIV-1 antigens and may serve as candidates for vaccine development.