scholarly journals Glycoprotein 96-Mediated Presentation of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Human Leukocyte Antigen Class I-Restricted Peptide and Humoral Immune Responses to HIV-1 p24

2009 ◽  
Vol 16 (11) ◽  
pp. 1595-1600 ◽  
Author(s):  
XiaoYan Gong ◽  
WeiWei Gai ◽  
JunQiang Xu ◽  
Wei Zhou ◽  
Po Tien
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Human Leukocyte ◽  
Adjuvant Effect ◽  
Leukocyte Antigen ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Immune Adjuvant ◽  
Hiv 1

ABSTRACT Viral antigens complexed to heat shock proteins (HSPs) can enhance antiviral immunity. The present study evaluated the immunogenicity of a novel human immunodeficiency virus type 1B′ (HIV-1B′)-specific, human leukocyte antigen A2 (HLA-A2)-restricted peptide (FLQSRPEPTA, Gag448-457) and the cellular immune adjuvant effect of HSP gp96 using the HLA-A2 transgenic mouse model. It was found that gp96 could augment cytotoxic-T-lymphocyte responses specific for the 10-mer peptide of HIV-1B′. This study also evaluated the humoral immune adjuvant effect of HSP gp96 and its N-terminal fragment (N336) and found that immunization of BALB/c mice with a mixture of gp96 or its N-terminal fragment and HIV-1 p24 antigen or with an p24-N336 fusion protein resulted in a significant increase in anti-HIV p24 antibody titer. These results demonstrate the possibility of using gp96 and its N fragment as adjuvants to augment cellular and humoral immune responses against HIV-1 infection.

scholarly journals Induction of Humoral Immune Responses following Vaccination with Envelope-Containing, Formaldehyde-Treated, Thermally Inactivated Human Immunodeficiency Virus Type 1

2005 ◽  
Vol 79 (8) ◽  
pp. 4927-4935 ◽  
Author(s):  
B. Poon ◽  
J. T. Safrit ◽  
H. McClure ◽  
C. Kitchen ◽  
J. F. Hsu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Thermal Treatment ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

scholarly journals Recombinant measles viruses expressing single or multiple antigens of human immunodeficiency virus (HIV-1) induce cellular and humoral immune responses

Vaccine ◽  
2009 ◽  
Vol 27 (25-26) ◽  
pp. 3299-3305 ◽  
Author(s):  
Matthias Liniger ◽  
Armando Zuniga ◽  
Teldja Neige Azzouz Morin ◽  
Behazine Combardiere ◽  
Rene Marty ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

2006 ◽  
Vol 80 (12) ◽  
pp. 6056-6060 ◽  
Author(s):  
Aleksandr Lazaryan ◽  
Elena Lobashevsky ◽  
Joseph Mulenga ◽  
Etienne Karita ◽  
Susan Allen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Leukocyte Antigen ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Leukocyte ◽  
Subtype C ◽  
Leukocyte Antigen ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties. We examined alleles of the HLA-B58 supertype (B58s) in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-seropositive Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P = 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P = 0.02) or B*5802-Cw*0602 (P = 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P = 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802 with slow (P = 0.06) and rapid (P = 0.003) disease progression, respectively. In neither population were B*1516-B*1517 alleles associated with more favorable responses. Overall, B58s alleles, individually or as part of an HLA-B-HLA-C haplotype, appeared to have a distinctive impact on HIV-1 infection among native Africans. As presently defined, B58s alleles cannot be considered uniformly protective against HIV/AIDS in every population.

scholarly journals A Glycoconjugate Antigen Based on the Recognition Motif of a Broadly Neutralizing Human Immunodeficiency Virus Antibody, 2G12, Is Immunogenic but Elicits Antibodies Unable To Bind to the Self Glycans of gp120

2008 ◽  
Vol 82 (13) ◽  
pp. 6359-6368 ◽  
Author(s):  
Rena D. Astronomo ◽  
Hing-Ken Lee ◽  
Christopher N. Scanlan ◽  
Ralph Pantophlet ◽  
Cheng-Yuan Huang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Neutralizing Antibody ◽  
Humoral Immune ◽  
Aids Vaccine ◽  
Humoral Immune Responses ◽  
Copy Numbers ◽  
Immunodeficiency Virus ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

ABSTRACT The glycan shield of human immunodeficiency virus type 1 (HIV-1) gp120 contributes to viral evasion from humoral immune responses. However, the shield is recognized by the HIV-1 broadly neutralizing antibody (Ab), 2G12, at a relatively conserved cluster of oligomannose glycans. The discovery of 2G12 raises the possibility that a carbohydrate immunogen may be developed that could elicit 2G12-like neutralizing Abs and contribute to an AIDS vaccine. We have previously dissected the fine specificity of 2G12 and reported that the synthetic tetramannoside (Man4) that corresponds to the D1 arm of Man9GlcNAc2 inhibits 2G12 binding to gp120 as efficiently as Man9GlcNAc2 itself, indicating the potential use of Man4 as a building block for creating immunogens. Here, we describe the development of neoglycoconjugates displaying variable copy numbers of Man4 on bovine serum albumin (BSA) molecules by conjugation to Lys residues. The increased valency enhances the apparent affinity of 2G12 for Man4 up to a limit which is achieved at ∼10 copies per BSA molecule, beyond which no further enhancement is observed. Immunization of rabbits with BSA-(Man4)14 elicits significant serum Ab titers to Man4. However, these Abs are unable to bind gp120. Further analysis reveals that the elicited Abs bind a variety of unbranched and, to a lesser extent, branched Man9 derivatives but not natural N-linked oligomannose containing the chitobiose core. These results suggest that Abs can be readily elicited against the D1 arm; however, potential differences in the presentation of Man4 on neoglycoconjugates, compared to glycoproteins, poses challenges for eliciting anti-mannose Abs capable of cross-reacting with gp120 and HIV-1.

scholarly journals Variability and Immunogenicity of Human Immunodeficiency Virus Type 1 p24 Gene Quasispecies

2000 ◽  
Vol 7 (3) ◽  
pp. 377-383 ◽  
Author(s):  
Johanna Iroegbu ◽  
Markus Birk ◽  
Una Lazdina ◽  
Anders Sönnerborg ◽  
Matti Sällberg
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Leukocyte ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Despite the conserved nature of the human immunodeficiency virus type 1 (HIV-1) gag gene, multiple quasispecies of the p24 gene coexist in HIV-1-infected patients. We cloned and sequenced 31 p24 genes from four HIV-1-infected patients. The intrapatient homology between the p24 genes ranged from 97.1 to 99.1%, whereas the interpatient homology ranged from 91.5 to 93.8%, suggesting a host-specific evolution. Synonymous and nonsynonymous nucleotide changes were evenly distributed in the p24 gene, with 27 and 28%, respectively, located within host human leukocyte antigen class I recognition sites. This would suggest only a minor influence from the host cytotoxic T-cell response on the evolution of the p24 gene. The importance of minor variations within p24 was analyzed by designing DNA-based immunogens from two distinct p24 quasispecies genes simultaneously derived from one patient. In plasmid-immunizedH-2b , H-2d , andH-2k haplotype mice, a clear influence from the host major histocompatibility complex was noted on the immune responses, fully consistent with those noted when a recombinant p24 protein is used as the immunogen. The two p24 DNA immunogens did not differ in their immunogenicity, indicating that the limited genetic variability (<1%) had little influence on the immune responses.

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