scholarly journals Immunological and Virological Analyses of Persons Infected by Human Immunodeficiency Virus Type 1 while Participating in Trials of Recombinant gp120 Subunit Vaccines

1998 ◽  
Vol 72 (2) ◽  
pp. 1552-1576 ◽  
Author(s):  
R. I. Connor ◽  
B. T. M. Korber ◽  
B. S. Graham ◽  
B. H. Hahn ◽  
D. D. Ho ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibody Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
The United States ◽  
Subunit Vaccines ◽  
Recombinant Gp120 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have studied 18 participants in phase I/II clinical trials of recombinant gp120 (rgp120) subunit vaccines (MN and SF-2) who became infected with human immunodeficiency virus type 1 (HIV-1) during the course of the trials. Of the 18 individuals, 2 had received a placebo vaccine, 9 had been immunized with MN rgp120, and seven had been immunized with SF-2 rgp120. Thirteen of the 18 infected vaccinees had received three or four immunizations prior to becoming infected. Of these, two were placebo recipients, six had received MN rgp120, and five had received SF-2 rgp120. Only 1 of the 11 rgp120 recipients who had multiple immunizations failed to develop a strong immunoglobulin G antibody response to the immunogen. However, the antibody response to rgp120 was transient, typically having a half-life of 40 to 60 days. No significant neutralizing activity against the infecting strain was detected in any of the infected individuals at any time prior to infection. Antibody titers in subjects infected despite vaccination and in noninfected subjects were not significantly different. Envelope-specific cytotoxic T-lymphocyte responses measured after infection were infrequent and weak in the nine vaccinees who were tested. HIV-1 was isolated successfully from all 18 individuals. Sixteen of these strains had a non-syncytium-inducing (NSI) phenotype, while two had a syncytium-inducing (SI) phenotype. NSI strains used the CCR5 coreceptor to enter CD4+ cells, while an SI strain from one of the vaccinees also used CXCR4. Viruses isolated from the blood of rgp120 vaccinees were indistinguishable from viruses isolated from control individuals in terms of their inherent sensitivity to neutralization by specific monoclonal antibodies and their replication rates in vitro. Furthermore, genetic sequencing of the envgenes of strains infecting the vaccinees did not reveal any features that clearly distinguished these viruses from contemporary clade B viruses circulating in the United States. Thus, despite rigorous genetic analyses, using various breakdowns of the data sets, we could find no evidence that rgp120 vaccination exerted selection pressure on the infecting HIV-1 strains. The viral burdens in the infected rgp120 vaccine recipients were also determined, and they were found to be not significantly different from those in cohorts of placebo-vaccinated and nonvaccinated individuals. In summary, we conclude that vaccination with rgp120 has had, to date, no obvious beneficial or adverse effects on the individuals we have studied.

scholarly journals Safety and Immunogenicity of Two Influenza Virus Subunit Vaccines, with or without MF59 Adjuvant, Administered to Human Immunodeficiency Virus Type 1-Seropositive and -Seronegative Adults

2007 ◽  
Vol 15 (2) ◽  
pp. 253-259 ◽  
Author(s):  
P. Durando ◽  
D. Fenoglio ◽  
A. Boschini ◽  
F. Ansaldi ◽  
G. Icardi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Influenza Virus ◽  
Antibody Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Geometric Mean ◽  
Subunit Vaccines ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The objective of this study was to evaluate and compare both the safety and tolerability and the humoral and cell-mediated immune responses for two influenza virus subunit vaccines, one with MF59 adjuvant (Fluad) and one without an adjuvant (Agrippal), in healthy and in human immunodeficiency virus type 1 (HIV-1)-infected adult individuals. To achieve this aim, an open, randomized, comparative clinical trial was performed during the 2005-2006 season. A total of 256 subjects were enrolled to receive one dose of vaccine intramuscularly. Blood samples were taken at the time of vaccination and at 1 and 3 months postvaccination. A good humoral antibody response was detected for both vaccines, meeting all the criteria of the Committee for Medical Products for Human Use. After Beyer's correction for prevaccination status, Fluad exhibited better immunogenicity than Agrippal, as shown from the analysis of the geometric mean titers, with significant differences for some virus strains; however, no definitive conclusions on the clinical significance of such results can be drawn, because the method used to estimate antibody response is currently nonstandard for influenza virus vaccines. Significant induction of an antigen-specific CD4+ T-lymphocyte proliferative response was detected at all time points after immunization, for both the vaccines, among HIV-1-seronegative subjects. This was different from what was observed for HIV-1-infected individuals. In this group, significance was not reached at 30 days postvaccination (T30) for those immunized with Agrippal. Also when data were compared between treatment groups, a clear difference in the response at T30 was observed in favor of Fluad (P = 0.0002). The safety profiles of both vaccines were excellent. For HIV-1-infected individuals, no significant changes either in viremia or in the CD4+ cell count were observed at any time point. The results showed good safety and immunogenicity for both vaccines under study for both uninfected and HIV-1-infected adults, confirming current recommendations for immunization of this high-risk category.

scholarly journals A Mutation in Human Immunodeficiency Virus Type 1 Protease, N88S, That Causes In Vitro Hypersensitivity to Amprenavir

2000 ◽  
Vol 74 (9) ◽  
pp. 4414-4419 ◽  
Author(s):  
Rainer Ziermann ◽  
Kay Limoli ◽  
Kalyan Das ◽  
Edward Arnold ◽  
Christos J. Petropoulos ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Salvage Therapy ◽  
The United States ◽  
Site Directed Mutagenesis ◽  
Cross Resistance ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Amprenavir (Agenerase, 141-W94, VX-478) is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PRI) recently approved for the treatment of HIV-1 infection in the United States. A major cause of treatment failure is the development of resistance to PRIs. One potential use for amprenavir is as salvage therapy for patients for whom treatment that includes one (or more) of the other four currently approved PRIs—saquinavir, indinavir, ritonavir, and nelfinavir—has failed. We evaluated the cross-resistance to amprenavir of viruses that evolved during treatment with the two most commonly prescribed PRIs, nelfinavir and indinavir. Unexpectedly, a dramatic increase in susceptibility (2.5- to 12.5-fold) was observed with 20 of 312 (6.4%) patient viruses analyzed. The most pronounced increases in susceptibility were strongly associated with an N88S mutation in protease. All viruses that carried the N88S mutation were hypersensitive to amprenavir. Site-directed mutagenesis studies confirmed the causal role of N88S in determining amprenavir hypersensitivity. The presence of the N88S mutation and associated amprenavir hypersensitivity may be useful in predicting an improved clinical response to amprenavir salvage therapy.

scholarly journals Human Immunodeficiency Virus Type 1 (HIV-1) Diversity at Time of Infection Is Not Restricted to Certain Risk Groups or Specific HIV-1 Subtypes

2004 ◽  
Vol 78 (13) ◽  
pp. 7279-7283 ◽  
Author(s):  
Manish Sagar ◽  
Erin Kirkegaard ◽  
E. Michelle Long ◽  
Connie Celum ◽  
Susan Buchbinder ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Risk Groups ◽  
The United States ◽  
Viral Envelope ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT African women frequently acquire several genetically distinct human immunodeficiency virus type 1 (HIV-1) variants from a heterosexual partner, whereas the acquisition of multiple variants appears to be rare in men. To determine whether newly infected individuals in other risk groups acquire genetically diverse viruses, we examined the viral envelope sequences in plasma samples from 13 women and 4 men from the United States infected with subtype B viruses and 10 men from Kenya infected with non-subtype B viruses. HIV-1 envelope sequences differed by more than 2% in three U.S. women, one U.S. man, and one Kenyan man near the time of seroconversion. These findings suggest that early HIV-1 genetic diversity is not exclusive to women from Africa or to infection with any particular HIV-1 subtype.

scholarly journals Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine

2004 ◽  
Vol 78 (5) ◽  
pp. 2586-2590 ◽  
Author(s):  
Udaykumar Ranga ◽  
Raj Shankarappa ◽  
Nagadenahalli B. Siddappa ◽  
Lakshmi Ramakrishna ◽  
Ramalingam Nagendran ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
The United States ◽  
Tat Protein ◽  
Subtype C ◽  
Monocyte Migration ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non-subtype C viruses and more than 90% of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.

scholarly journals 4E10-Resistant Variants in a Human Immunodeficiency Virus Type 1 Subtype C-Infected Individual with an Anti-Membrane-Proximal External Region-Neutralizing Antibody Response

2007 ◽  
Vol 82 (5) ◽  
pp. 2367-2375 ◽  
Author(s):  
Elin S. Gray ◽  
Penny L. Moore ◽  
Frederic Bibollet-Ruche ◽  
Hui Li ◽  
Julie M. Decker ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibody Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Neutralizing Antibody ◽  
Subtype C ◽  
External Region ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The broadly neutralizing monoclonal antibody (MAb) 4E10 recognizes a linear epitope in the C terminus of the membrane-proximal external region (MPER) of gp41. This epitope is particularly attractive for vaccine design because it is highly conserved among human immunodeficiency virus type 1 (HIV-1) strains and neutralization escape in vivo has not been observed. Multiple env genes were cloned from an HIV-1 subtype C virus isolated from a 7-year-old perinatally infected child who had anti-MPER neutralizing antibodies. One clone (TM20.13) was resistant to 4E10 neutralization as a result of an F673L substitution in the MPER. Frequency analysis showed that F673L was present in 33% of the viral variants and in all cases was linked to the presence of an intact 2F5 epitope. Two other envelope clones were sensitive to 4E10 neutralization, but TM20.5 was 10-fold less sensitive than TM20.6. Substitutions at positions 674 and 677 within the MPER rendered TM20.5 more sensitive to 4E10 but had no effect on TM20.6. Using chimeric and mutant constructs of these two variants, we further demonstrated that the lentivirus lytic peptide-2 domain in the cytoplasmic tail affected the accessibility of the 4E10 epitope, as well as virus infectivity. Collectively, these genetic changes in the face of a neutralizing antibody response to the MPER strongly suggested immune escape from antibody responses targeting this region.

scholarly journals Characterization of Antibody Responses Elicited by Human Immunodeficiency Virus Type 1 Primary Isolate Trimeric and Monomeric Envelope Glycoproteins in Selected Adjuvants

2006 ◽  
Vol 80 (3) ◽  
pp. 1414-1426 ◽  
Author(s):  
Y. Li ◽  
K. Svehla ◽  
N. L. Mathy ◽  
G. Voss ◽  
J. R. Mascola ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibody Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Neutralizing Antibodies ◽  
V3 Loop ◽  
Homologous Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We previously reported that soluble, stable YU2 gp140 trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein immunogens could elicit improved breadth of neutralization against HIV-1 isolates compared to monomeric YU2 gp120 proteins. In this guinea pig immunization study, we sought to extend these data and determine if adjuvant could quantitatively or qualitatively alter the neutralizing response elicited by trimeric or monomeric immunogens. Consistent with our earlier studies, the YU2 gp140 immunogens elicited higher-titer neutralizing antibodies against homologous and heterologous isolates than those elicited by monomeric YU2 gp120. Additionally, the GlaxoSmithKline family of adjuvants AS01B, AS02A, and AS03 induced higher levels of neutralizing antibodies compared to emulsification of the same immunogens in Ribi adjuvant. Further analysis of vaccine sera indicated that homologous virus neutralization was not mediated by antibodies to the V3 loop, although V3 loop-directed neutralization could be detected for some heterologous isolates. In most gp120-inoculated animals, the homologous YU2 neutralization activity was inhibited by a peptide derived from the YU2 V1 loop, whereas the neutralizing activity elicited by YU2 gp140 trimers was much less sensitive to V1 peptide inhibition. Consistent with a less V1-focused antibody response, sera from the gp140-immunized animals more efficiently neutralized heterologous HIV-1 isolates, as determined by two distinct neutralization formats. Thus, there appear to be qualitative differences in the neutralizing antibody response elicited by YU2 gp140 compared to YU2 monomeric gp120. Further mapping analysis of more conserved regions of gp120/gp41 may be required to determine the neutralizing specificity elicited by the trimeric immunogens.

scholarly journals Early Virus Clearance and Delayed Antibody Response in a Case of Coronavirus Disease 2019 (COVID-19) With a History of Coinfection With Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

2020 ◽  
Vol 71 (16) ◽  
pp. 2233-2235 ◽  
Author(s):  
Juanjuan Zhao ◽  
Xuejiao Liao ◽  
Haiyan Wang ◽  
Lanlan Wei ◽  
Mingzhao Xing ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antibody Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
First Case ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract The effect of host immune status on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Here, we report the first case of coronavirus disease 2019 (COVID-19) with human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus coinfection, who showed a persistently negative SARS-CoV-2 RNA test but delayed antibody response in the plasma. This case highlights the influence of HIV-1–induced immune dysfunction on early SARS-CoV-2 clearance.

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