Bioactive fragment of human interleukin-1 b (163-171) modulates the immune response to synthetic peptides of RESA of Plasmodium falciparum

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.

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“…Several reports from our lab also confirm these findings with CS protein of Plasmodium vivax [25-27]. …”

Section: Discussionsupporting

confidence: 84%

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

Agrawal

Haq²,

Hanson

et al. 2003

J Immune Based Ther Vaccines

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“…IL-1 is known to have diverse immunological functions besides acting as a first costimulatory molecule during T cell activation. IL-1 possess inflammatory and adjuvant property, so we used a bioactive segment of IL-1 (IL-113) to modulate the immunogenic function of an asexual blood stage antigen of P. falciparum (62) as well as modulating the immunogenicity of HIV peptide antigens (63). It was seen that a nine amino acid fragment of ILl could substitute the entire IL-1 molecule in mounting an effective immune response against these candidate antigens.…”

Section: Other Adjuvants Cytokinesmentioning

confidence: 99%

New age adjuvants and delivery systems for subunit vaccines

Koduri

Manocha

Sabhnani

et al. 2000

Indian J Clin Biochem

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The dramatic advancements in the field of vaccinology has led to the formulation of chemically well defined vaccines composed of synthetic peptides and recombinant proteins derived from the immunologically dominant regions of the pathogens. Though these subunit vaccines are safer compared to the traditional vaccines they are known to be poorly immunogenic. This necessitates the use of adjuvants to enhance the immunogenicity of these vaccine formulations. The most common adjuvant for human use is alum. Research in the past has focused on the development of systemic immunity using conventional immunization protocols. In the present era, the emphasis is on the development and formulation of alternative adjuvants and delivery systems in generating systemic as well as mucosal immunity. This review mainly focuses on a variety of adjuvants (particulate as well as non-particulate) used with protective antigens of HIV, malaria, plague, leprosy using modified delivery vehicles. The experience of our laboratory and other researchers in this field clearly proves that these new age adjuvants and delivery systems undoubtedly generate enhanced immune response -both humoral and cell mediated. The choice of antigens, the nature of adjuvant used and the mode of delivery employed have a profound effect on the type of immune response generated. Besides the quantity, the quality of the antibodies generated also play a vital role in protection against these diseases. Some of the adjuvants and delivery systems used promoted high titre and affinity antibodies, which were shown to be cytophilic in nature, an important criteria in providing protection to the host. Thus the studies on these adjuvants/ delivery systems with respect to various infectious diseases indicate their active role in efficient modulation of immune response along with safety and permissiblity.

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“…Previous studies in our laboratory have established the signi®cant role of immunomodulators like polytuftsin or the bioactive fragment of human IL-1b in conjunction with liposomal delivery of synthetic peptides of ring-infected erythrocyte surface antigen (RESA) for developing eective subunit formulations against malaria [7,17,18,33].…”

Section: Introductionmentioning

confidence: 99%

Inducing protective antibodies against ring-infected erythrocyte surface peptide antigen of Plasmodium falciparum using immunostimulating complex (ISCOMs) delivery

Chopra

Biswas

Thomas

et al. 2000

Medical Microbiology and Immunology

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In the present study, synthetic peptides (EENVEHDA)2 [(oc)2] and (DDEHVEEPTVA)2 [(un)2] of ring-infected erythrocyte surface antigen (RESA) of Plasmodlium filciparum were linked with palmitic acid and entrapped in immunostimulating complexes (ISCOMs). The immunogenicity of the peptide(s) and mixture of peptides were studied in mice with different genetic background. Peptide(s) entrapped in ISCOMs using a low-dose immunization strategy generated high-titer as well as high-affinity antibodies. Interestingly, no genetic restriction of the immune response was observed in any of the strains studied. The IgG subclass pattern with the peptide(s) showed predominately IgG2a/2b isotypes, while with the mixed peptide formulation, (un)2-specific IgG isotype pattern showed induction of both IgG1 and IgG2a/2b isotypes. These cytophilic antibodies inhibited the ring as well as schizont stage and total parasite growth during in vitro merozoite reinvasion inhibition study. In the mixed peptide preparation, the same pattern of immune response was achieved as that of individual peptide(s) using ISCOMs delivery. Therefore, the entrapment of otherwise poorly immunogenic synthetic peptides in ISCOMs resulted in increased immunogenicity followed by strong secondary response and can be adopted for developing subunit immunogen formulation against malarial parasite.

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Bioactive fragment of human interleukin-1 b (163-171) modulates the immune response to synthetic peptides of RESA of Plasmodium falciparum

Cited by 4 publications

References 26 publications

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

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

New age adjuvants and delivery systems for subunit vaccines

Inducing protective antibodies against ring-infected erythrocyte surface peptide antigen of Plasmodium falciparum using immunostimulating complex (ISCOMs) delivery

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