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

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.

Co-delivery of a CD4 T cell helper epitope via covalent liposome attachment with a surface-arrayed B cell target antigen fosters higher affinity antibody responses

“…Studies showed that the properties of liposomes such as size, lipid composition and antigen encapsulation methods, etc. can skew Th1/Th2 antibody responses [28] , [29] , [48] , [49] , [16] . In our experimental setting, the only variable is the methods of LACK peptide formulation in liposome vaccine.…”

Inclusion of the Bovine Neutrophil Beta-Defensin 3 with Glycoprotein D of Bovine Herpesvirus 1 in a DNA Vaccine Modulates Immune Responses of Mice and Cattle

“…Our data may be explained, however, by the findings of others. Reports have suggested that while Th1-type cyto- kines exert an overall negative effect on systemic humoral responses (79,81), they can have a positive effect on the magnitude of neutralizing antibody responses (82), and that neutralizing antibody responses can occur concurrent with induction of Th1-polarized responses (83)(84)(85). In particular, our results (VN antibody concurrent with induction of CTL) with this defensin-antigen fusion construct in cattle bears striking similarity to the results obtained when in the mouse model, an experimental DNA vaccine expressing murine beta-defensin 2 (mBD2) as a fusion with the gp120 antigen of HIV-1 induced systemic and mucosal CTLs and neutralizing antibody to the HIV-1 envelope protein in i.d.…”

Nanoscience versus Viruses: The SARS‐CoV‐2 Case

“…[ 74 ] It was found that the experimental vaccine formulations based on ISCOMs enable effective prevention and spreading of infectious diseases caused by various pathogens such as viruses, retroviruses, parasites, and bacteria. So far, antigens derived from influenza, [ 149 ] herpes simplex virus, [ 150 ] HIV‐1, [ 151 ] and Newcastle disease [ 148 ] have been used to formulate ISCOMs.…”