Quantitation of antigen-specific immune responses in human immunodeficiency virus (HIV)-infected individuals by limiting dilution analysis

1992 ◽  
Vol 12 (3) ◽  
pp. 216-224 ◽  
Author(s):  
Steffanie Sabbaj ◽  
Michael F. Para ◽  
Robert J. Fass ◽  
Patrick W. Adams ◽  
Charles G. Orosz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Limiting Dilution Analysis ◽  
Immunodeficiency Virus ◽  
Limiting Dilution

scholarly journals Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities.

1991 ◽  
Vol 174 (6) ◽  
pp. 1593-1600 ◽  
Author(s):  
R A Koup ◽  
C A Pikora ◽  
K Luzuriaga ◽  
D B Brettler ◽  
E S Day ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Effector Cell ◽  
Mononuclear Cells ◽  
Limiting Dilution Analysis ◽  
Activated State ◽  
Immunodeficiency Virus ◽  
Limiting Dilution

The presence of cytotoxic T lymphocytes (CTL) to the gag antigens of human immunodeficiency virus (HIV) has been described in infected populations. We found that the majority of this immune response as measured in bulk CTL assays of unstimulated peripheral blood mononuclear cells (PBMC) is directed against the p24 component of the p55 gag precursor protein. Using limiting dilution analysis of this effector cell population we confirm that the majority of activated gag-specific CTL circulating in the PBMC of infected hemophilic patients are directed at p24 determinants and are present at frequencies of 1/36,000 to 1/86,000 lymphocytes. By performing in vitro stimulation after limiting dilution, the precursor population of gag-specific CTL are characterized and quantitated. HIV gag-specific CTL precursors are identified at frequencies of 1/1700 to 1/17,000 lymphocytes and are made up of cells with both p17 and p24 specificities. No HIV gag-specific CTL precursor cells are identified in the PBMC of HIV-uninfected individuals. These studies demonstrate that CTL directed at both p17 and p24 determinants make up the cellular immune repertoire in HIV-infected individuals but that only the p24-specific CTL are routinely found in an activated state in the circulation.

scholarly journals Optimization of Human Immunodeficiency Virus Gag Expression by Newcastle Disease Virus Vectors for the Induction of Potent Immune Responses

2008 ◽  
Vol 83 (2) ◽  
pp. 584-597 ◽  
Author(s):  
Elena Carnero ◽  
Wenjing Li ◽  
Antonio V. Borderia ◽  
Bruno Moltedo ◽  
Thomas Moran ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Insertion Site ◽  
Gag Protein ◽  
Immunodeficiency Virus

ABSTRACT One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8+ T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.

scholarly journals Quantitating Effector and Regulatory T Lymphocytes in Immune Responses by Limiting Dilution Analysis Modeling

2005 ◽  
Vol 174 (6) ◽  
pp. 3421-3431 ◽  
Author(s):  
Thierry Bonnefoix ◽  
Philippe Bonnefoix ◽  
Pascal Perron ◽  
Jian-Qing Mi ◽  
Wan Fai Ng ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Regulatory T Lymphocytes ◽  
Limiting Dilution Analysis ◽  
Limiting Dilution

scholarly journals Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

2005 ◽  
Vol 86 (2) ◽  
pp. 339-348 ◽  
Author(s):  
L. Lopalco ◽  
C. Barassi ◽  
C. Paolucci ◽  
D. Breda ◽  
D. Brunelli ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Serum Samples ◽  
Predictive Values ◽  
Asian Populations ◽  
Immunodeficiency Virus ◽  
Hiv Exposure ◽  
Route Of Exposure ◽  
Humoral Responses ◽  
Hiv 1

Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus–cell interactions, IgG to CD4–gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4–gp120 complex) were extremely significant predictors of HIV exposure (P<0·0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.

scholarly journals Assessment of Antibody Response Elicited by a 7-valent Pneumococcal Conjugate Vaccine in Pediatric Human Immunodeficiency Virus Infection

2005 ◽  
Vol 12 (1) ◽  
pp. 165-170 ◽  
Author(s):  
David Tarragó ◽  
Julio Casal ◽  
Jesús Ruiz-Contreras ◽  
J. Tomás Ramos ◽  
Pablo Rojo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Correlation Coefficients ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immunodeficiency Virus ◽  
Vaccine Immunogenicity ◽  
Functional Antibodies

ABSTRACT We investigated antibody responses against pneumococci of serotypes 6B, 14, and 23F in 56 children and adolescents with perinatal human immunodeficiency virus (HIV) infection who were vaccinated with 7-valent pneumococcal conjugate vaccine. Overall immune responses differed greatly between serotypes. Correlation coefficients between immunoglobulin G (IgG) measured by enzyme-linked immunosorbent assay (ELISA) and functional antibodies measured by a flow cytometry opsonophagocytosis assay (OPA) varied with serotype and time points studied. After 3 months of administering a second PCV7 dose we got the highest correlation (with significant r values of 0.754, 0.414, and 0.593 for serotypes 6B, 14, and 23F, respectively) but no significant increase in IgG concentration and OPA titers compared to the first dose. We defined a responder to a serotype included in the vaccine with two criteria: frequency of at least twofold OPA and ELISA increases for each serotype and frequency of conversion from negative to positive OPA levels. Responders varied from 43.9% to 46.3%, 28.5% to 50.0%, and 38.0% to 50.0% for serotypes 6B, 14, and 23F, respectively, depending on the response criterion. The present research highlights the importance of demonstrating vaccine immunogenicity with suitable immunological endpoints in immunocompromised patients and also the need to define how much antibody is required for protection from different serotypes, since immunogenicity differed significantly between serotypes.

scholarly journals DNA Vaccination with the Human Immunodeficiency Virus Type 1 SF162ΔV2 Envelope Elicits Immune Responses That Offer Partial Protection from Simian/Human Immunodeficiency Virus Infection to CD8+ T-Cell-Depleted Rhesus Macaques

2001 ◽  
Vol 75 (3) ◽  
pp. 1547-1550 ◽  
Author(s):  
S. Cherpelis ◽  
I. Shrivastava ◽  
A. Gettie ◽  
X. Jin ◽  
D. D. Ho ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Cd8 T Cell ◽  
Dna Immunization ◽  
Plasma Virus ◽  
Partial Protection ◽  
Immunodeficiency Virus

ABSTRACT DNA immunization of macaques with the SF162ΔV2 envelope elicited lymphoproliferative responses and potent neutralizing antibodies. The animals were depleted of their CD8+ T lymphocytes and then challenged intravenously with SHIV162P4. Compared to unvaccinated animals, the vaccinated macaques had lower peak viremia levels, rapidly cleared plasma virus, and showed delayed seroconversion.

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