scholarly journals The Results of Clinical Trials of Recombinant Vaccine Virus, MVA Strain, Expressing Genes of Human Immunodeficiency Virus

2021 ◽  
pp. 13-22
Author(s):  
L. F. Stovba ◽  
S. A. Mel’nikov ◽  
D. I. Paveli’ev ◽  
V. T. Krotkov ◽  
N. K. Chernikova ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Immune Responses ◽  
Hiv Infection ◽  
Vaccine Virus ◽  
Viral Reservoirs ◽  
Humoral Immune ◽  
Number Of Patients ◽  
Immunodeficiency Virus ◽  
The Usa

Although successes in antiretroviral therapy (ART) turned AIDS from lethal illness into sluggishly progressing disease, its prevention and treatment remain one of the most socially significant concerns. The increase in the number of patients infected with human immunodeficiency virus (HIV), especially in the USA, South America and Europe, determines the need in creating a vaccine against this disease. Existing vaccination practice has demonstrated efficiency of priming/boosting scheme for the development of immune responses. As anti-vector immunity of priming vector can constrain the response to boosting immunization with the same vaccine, heterologous priming/boosting vector constructs are used. An ideal AIDS vaccine would prevent virus dissemination and control viral replication, but it also must be safe for HIV-infected contingent. The vaccination of HIV-infected individuals is used for enhancing immune-mediated elimination of persistently HIV-infected CD4+ Т-cells during long-term ART in order to purge the latently infected viral reservoirs. The paper considers the results of clinical trials of DNA-anti-HIV/AIDS vaccines and recombinant MVA strain of vaccinia virus, expressing different combination of HIV genes, which demonstrated the safety and tolerability both, in HIV-infected and non-HIV-infected volunteers. All implemented schedules of vaccination induced cell-mediated and humoral immune responses in all volunteers. And though there are no data on acquiring AIDS by HIV-uninfected volunteers from groups at low risk of HIV-infection, there are no grounds to conclude the sufficiency of induced protection for the prevention of possible HIV 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.

Aberrant and Unstable Expression of Immunoglobulin Genes in Persons Infected With Human Immunodeficiency Virus

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1317-1323 ◽  
Author(s):  
Alberto Bessudo ◽  
Laura Rassenti ◽  
Diane Havlir ◽  
Douglas Richman ◽  
Ellen Feigal ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Healthy Adults ◽  
Immunoglobulin Genes ◽  
Expression Levels ◽  
Humoral Immune ◽  
Immunodeficiency Virus ◽  
Vh Gene ◽  
American Society ◽  
Over Time

We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VHgene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VHgene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens. © 1998 by The American Society of Hematology.

Aberrant and Unstable Expression of Immunoglobulin Genes in Persons Infected With Human Immunodeficiency Virus

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1317-1323 ◽  
Author(s):  
Alberto Bessudo ◽  
Laura Rassenti ◽  
Diane Havlir ◽  
Douglas Richman ◽  
Ellen Feigal ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Healthy Adults ◽  
Immunoglobulin Genes ◽  
Expression Levels ◽  
Humoral Immune ◽  
Immunodeficiency Virus ◽  
Vh Gene ◽  
American Society ◽  
Over Time

Abstract We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VHgene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VHgene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens. © 1998 by The American Society of Hematology.

scholarly journals Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Ria Goswami ◽  
Ashley N. Nelson ◽  
Joshua J. Tu ◽  
Maria Dennis ◽  
Liqi Feng ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Short Term ◽  
Analytical Treatment ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus

ABSTRACT To achieve long-term viral remission in human immunodeficiency virus (HIV)-infected children, novel strategies beyond early antiretroviral therapy (ART) will be necessary. Identifying clinical predictors of the time to viral rebound upon ART interruption will streamline the development of novel therapeutic strategies and accelerate their evaluation in clinical trials. However, identification of these biomarkers is logistically challenging in infants, due to sampling limitations and the potential risks of treatment interruption. To facilitate the identification of biomarkers predicting viral rebound, we have developed an infant rhesus macaque (RM) model of oral simian-human immunodeficiency virus (SHIV) SHIV.CH505.375H.dCT challenge and analytical treatment interruption (ATI) after short-term ART. We used this model to characterize SHIV replication kinetics and virus-specific immune responses during short-term ART or after ATI and demonstrated plasma viral rebound in 5 out of 6 (83%) infants. We observed a decline in humoral immune responses and partial dampening of systemic immune activation upon initiation of ART in these infants. Furthermore, we monitored SHIV replication and rebound kinetics in infant and adult RMs and found that both infants and adults demonstrated equally potent virus-specific humoral immune responses. Finally, we validated our models by confirming a well-established correlate of the time to viral rebound, namely, the pre-ART plasma viral load, as well as identified additional potential humoral immune correlates. Thus, this model of infant ART and viral rebound can be used and further optimized to define biomarkers of viral rebound following long-term ART as well as to preclinically assess novel therapies to achieve a pediatric HIV functional cure. IMPORTANCE Novel interventions that do not rely on daily adherence to ART are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong ART. Considering the risks and expense associated with ART interruption trials, the identification of biomarkers of viral rebound will prioritize promising therapeutic intervention strategies, including anti-HIV Env protein therapeutics. However, comprehensive studies to identify those biomarkers are logistically challenging in human infants, demanding the need for relevant nonhuman primate models of HIV rebound. In this study, we developed an infant RM model of oral infection with simian-human immunodeficiency virus expressing clade C HIV Env and short-term ART followed by ATI, longitudinally characterizing the immune responses to viral infection during ART and after ATI. Additionally, we compared this infant RM model to an analogous adult RM rebound model and identified virologic and immunologic correlates of the time to viral rebound after ATI.

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.

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