Faculty Opinions recommendation of Co-administration of CH31 broadly neutralizing antibody does not affect development of vaccine-induced anti-HIV-1 envelope antibody responses in infant Rhesus macaques.

2019 ◽  
Author(s):  
Antu Dey
Keyword(s):  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Infant Rhesus

scholarly journals Immunogenicity, safety and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

2020 ◽  
Author(s):  
Blasi Maria ◽  
Negri Donatella ◽  
Saunders O Kevin ◽  
Baker J Erich ◽  
Stadtler Hannah ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Lentiviral Vector ◽  
Rhesus Macaques ◽  
Infected Individual ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Safety And Efficacy ◽  
Broadly Neutralizing Antibody ◽  
Env Protein ◽  
Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study we report the immunogenicity, safety and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Env induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/- protein immunizations using the same sequential envelopes. Compared to monkeys immunized with vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six month after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Our results show that while IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms, the use of non-stabilized sequential envelope trimers did not induce broadly neutralizing antibody responses.

scholarly journals Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Maria Blasi ◽  
Donatella Negri ◽  
Kevin O. Saunders ◽  
Erich J. Baker ◽  
Hannah Stadtler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Lentiviral Vector ◽  
Rhesus Macaques ◽  
Infected Individual ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Safety And Efficacy ◽  
Env Protein ◽  
Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms.

scholarly journals Peripheral Membrane Interactions Boost the Engagement by an Anti-HIV-1 Broadly Neutralizing Antibody

2017 ◽  
Vol 292 (13) ◽  
pp. 5571-5583 ◽  
Author(s):  
Edurne Rujas ◽  
José M. M. Caaveiro ◽  
Sara Insausti ◽  
Miguel García-Porras ◽  
Kouhei Tsumoto ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Membrane Interactions ◽  
Broadly Neutralizing Antibody ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Lower Broadly Neutralizing Antibody Responses in Female Versus Male HIV-1 Infected Injecting Drug Users

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 384
Author(s):  
Zelda EULER ◽  
Tom L. VAN DEN KERKHOF ◽  
Roger D. KOUYOS ◽  
Damien C. TULLY ◽  
Todd M. ALLEN ◽  
...  
Keyword(s):  
Drug Users ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Injecting Drug Users ◽  
Antibody Responses ◽  
Multiple Factors ◽  
Efficacy Trials ◽  
Female Idus ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

Understanding the factors involved in the development of broadly neutralizing antibody (bNAb) responses in natural infection can guide vaccine design aimed at eliciting protective bNAb responses. Most of the studies to identify and study the development of bNAb responses have been performed in individuals who had become infected via homo- or heterosexual HIV-1 transmission; however, the prevalence and characteristics of bNAb responses in injecting drug users (IDUs) have been underrepresented. We retrospectively studied the prevalence of bNAb responses in HIV-1 infected individuals in the Amsterdam Cohort, including 50 male and 35 female participants who reported injecting drug use as the only risk factor. Our study revealed a significantly lower prevalence of bNAb responses in females compared to males. Gender, transmission route and CD4+ count at set point, but not viral load, were independently associated with the development of bNAb responses in IDUs. To further explore the influences of gender in the setting of IDU, we also looked into the Swiss 4.5k Screen. There we observed lower bNAb responses in female IDUs as well. These results reveal that the emergence of bNAbs may be dependent on multiple factors, including gender. Therefore, the effect of gender on the development of bNAb responses is a factor that should be taken into account when designing vaccine efficacy trials.

scholarly journals Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193773 ◽  
Author(s):  
Nuria González ◽  
Krisha McKee ◽  
Rebecca M. Lynch ◽  
Ivelin S. Georgiev ◽  
Laura Jimenez ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

scholarly journals Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Nature ◽  
2018 ◽  
Vol 561 (7723) ◽  
pp. 406-410 ◽  
Author(s):  
Roger D. Kouyos ◽  
◽  
Peter Rusert ◽  
Claus Kadelka ◽  
Michael Huber ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

scholarly journals Bridging Vaccine-Induced HIV-1 Neutralizing and Effector Antibody Responses in Rabbit and Rhesus Macaque Animal Models

2019 ◽  
Vol 93 (10) ◽  
Author(s):  
Justin Pollara ◽  
Dorothy I. Jones ◽  
Tori Huffman ◽  
R. Whitney Edwards ◽  
Maria Dennis ◽  
...  
Keyword(s):  
Animal Models ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Rabbit Model ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Target Cells ◽  
Human Natural Killer Cells ◽  
Hiv 1

ABSTRACTStudies in animal models are essential prerequisites for clinical trials of candidate HIV vaccines. Small animals, such as rabbits, are used to evaluate promising strategies prior to further immunogenicity and efficacy testing in nonhuman primates. Our goal was to determine how HIV-specific vaccine-elicited antibody responses, epitope specificity, and Fc-mediated functions in the rabbit model can predict those in the rhesus macaque (RM) model. Detailed comparisons of the HIV-1-specific IgG response were performed on serum from rabbits and RM given identical modified vaccinia virus Ankara-prime/gp120-boost immunization regimens. We found that vaccine-induced neutralizing antibody, gp120-binding antibody levels and immunodominant specificities, antibody-dependent cellular phagocytosis of HIV-1 virions, and antibody-dependent cellular cytotoxicity (ADCC) responses against gp120-coated target cells were similar in rabbits and RM. However, we also identified characteristics of humoral immunity that differed across species. ADCC against HIV-infected target cells was elicited in rabbits but not in RM, and we observed differences among subdominantly targeted epitopes. Human Fc receptor binding assays and analysis of antibody-cell interactions indicated that rabbit vaccine-induced antibodies effectively recruited and activated human natural killer cells, while vaccine-elicited RM antibodies were unable to activate either human or RM NK cells. Thus, our data demonstrate that both Fc-independent and Fc-dependent functions of rabbit antibodies can be measured with commonly usedin vitroassays; however, the ability of immunogenicity studies performed in rabbits to predict responses in RM will vary depending on the particular immune parameter of interest.IMPORTANCENonneutralizing antibody functions have been associated with reduced infection risk, or control of virus replication, for HIV-1 and related viruses. It is therefore critical to evaluate development of these responses throughout all stages of preclinical testing. Rabbits are conventionally used to evaluate the ability of vaccine candidates to safely elicit antibodies that bind and neutralize HIV-1. However, it remained unexplored how effectively rabbits model the development of nonneutralizing antibody responses in primates. We administered identical HIV-1 vaccine regimens to rabbits and rhesus macaques and performed detailed comparisons of vaccine-induced antibody responses. We demonstrated that nonneutralizing HIV-specific antibody responses can be studied in the rabbit model and have identified aspects of these responses that are common, and those that are unique, to rabbits and rhesus macaques. Our findings will help determine how to best utilize preclinical rabbit and rhesus macaque models to accelerate HIV vaccine candidate testing in human trials.

scholarly journals Functional Contacts between MPER and the Anti-HIV-1 Broadly Neutralizing Antibody 4E10 Extend into the Core of the Membrane

2017 ◽  
Vol 429 (8) ◽  
pp. 1213-1226 ◽  
Author(s):  
Edurne Rujas ◽  
Sara Insausti ◽  
Miguel García-Porras ◽  
Rubén Sánchez-Eugenia ◽  
Kouhei Tsumoto ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
The Core ◽  
Antibody 4E10 ◽  
Broadly Neutralizing Antibody ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals HIV-1-Specific CAR-T Cells With Cell-Intrinsic PD-1 Checkpoint Blockade Enhance Anti-HIV Efficacy in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengtao Jiang ◽  
Huitong Liang ◽  
Hanyu Pan ◽  
Yue Liang ◽  
Hua Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Lines ◽  
Neutralizing Antibody ◽  
Single Chain ◽  
Functional Cure ◽  
Car T Cells ◽  
Car T ◽  
Broadly Neutralizing Antibody ◽  
Anti Hiv ◽  
Hiv 1

Adoptive cellular immunotherapy therapy using broadly neutralizing antibody-based chimeric antigen receptor-T cells (bNAb-based CAR-T) has shown great potency and safety for the functional cure of HIV. The efficacy of bNAb-based CAR-T cells could be compromised by adaptive resistance during HIV chronic infection according to the phenomenon that cellular exhaustion was observed in endogenous cytotoxic T-lymphocytes (CTLs) along with upregulated expression of PD−1. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells (PBMCs) and a 3BNC117-DNR CAR (3BD CAR) construct that enables the expression of PD-1 dominant negative receptor (DNR) and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV envelope glycoprotein (Env). Compared with HIV CAR expression alone, 3BD CAR-T cells displayed potent lytic and functional responses to Env-expressing cell lines and HIV-infected CD4+ T cells. Moreover, 3BD CAR-T cells can kill HIV-latently-infected cell lines, which are reactivated by the secretory cytokines of effector cells followed by contact with initial HIV-expressing fraction. Furthermore, bioluminescence imaging indicated that 3BD CAR-T cells displayed superior anti-HIV function in an HIV NCG mouse model of transplanting Env+/PD-L1+ cells (LEL6). These studies suggested that our proposed combinational strategy of HIV CAR-T therapy with PD-1 blockade therapy is feasible and potent, making it a promising therapeutic candidate for HIV functional cure.

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