A Phase I Multicenter Double-blind Placebo Controlled Dose Escalation Trial of an Adjuvanted Anti-CD40 mAb Fused to Env GP140 HIV Clade C ZM-96 (CD40.HIVRI.Env) Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Participants

Multicenter double-blind placebo controlled phase I dose-escalation trial that will be conducted in France and Switzerland to evaluate different dose levels of CD40.HIVRI.Env (adjuvanted with Hiltonol) alone and in co-administration with DNA-HIV-PT123.
A total of 72 eligible healthy participants will be recruited into 6 groups. Within each group, participants will be randomized in a double blind manner to active intervention or placebo in a 5:1 ratio. Enrolment into a given group (other than group "Solo 0.3") will open sequentially depending on the " go-criterion " based on the safety data of the preceding group(s).
The primary objective is to assess the safety of three dose levels of CD40.HIVRI.Env (0.3; 1; 3 mg) adjuvanted with Poly-ICLC (Hiltonol®), alone and in combination with DNA-HIV-PT123, administered at weeks 0, 4 and 24 in healthy participants.
Secondary objectives are to assess the capacity of poly-ICLC-adjuvanted CD40.HIVRI.Env alone and in combination with DNA-HIV-PT123 to elicit immune responses against HIV (immunogenicity):
* Humoral (antibody) responses ;
* B-cell responses ;
* T-cell responses.

开始日期2021-03-29

申办/合作机构

ANRS, Emerging Infectious Diseases

NCT02376582 / Completed临床1期IIT

A Phase I Double Blind Placebo-controlled Clinical Trial to Evaluate the Safety and Immunogenicity of the Combination of DNA-HIV-PT123 and AIDSVAX®B/Ein HIV-1-uninfected Adult Participants With or Without Underlying Schistosoma Mansoni Infection

The primary objective of the proposed phase I trial is to evaluate the safety and tolerability of DNA-HIV-PT123 and AIDSVAX®B/E combination regimen. Though both DNA-HIV-PT123 and AIDSVAX®B/E and the combination of the two vaccines have been evaluated in humans and have shown to be safe and well tolerated, this is the first time the combination regimen is being evaluated in HIV-1 uninfected African populations with and without S. mansoni. The secondary objective of the trial is to evaluate the effect of S. mansoni infection on the immunogenicity of the combination of DNA-HIV-PT123 and AIDSVAX® B/E vaccine regimen. Successful vaccination against most viruses requires efficient Th1 response. There is evidence that helminth infections skew the host immune system of human and animals to T-helper type 2 (Th2) and induce immunosuppression. Therefore, there is a potential that helminth infected populations may not generate the desired immune responses to vaccines designed to drive Th1-type and cytotoxic T-cell responses.
Furthermore, the influence of helminth infections on the development of protective antibody responses remains unclear. Limited data in animal models suggests that worm infections reduced efficacy of vaccines.
The proposed vaccine trial will generate safety, tolerability and immunogenicity data of a vaccination regimen with simultaneous administration of a candidate HIV DNA vaccine (DNA-HIV-PT123) and a gp120 protein vaccine (AIDSVAX®B/E). This will be the first HIV vaccine trial to prospectively evaluate the impact of the S. mansoni infection on safety and immune responses to HIV vaccines.

开始日期2014-09-01

申办/合作机构

EuroVacc Foundation

[+3]

NCT01799954 / Completed临床1期IIT

A Phase 1 Double Blind Placebo-controlled Clinical Trial to Evaluate the Safety and to Compare the Priming Ability of NYVAC Alone Versus NYVAC + AIDSVAX® B/E, and DNA Alone Versus DNA + AIDSVAX® B/E When Followed by NYVAC + AIDSVAX® B/E Boosts in Healthy, HIV-1-uninfected Adult Participants

This study will evaluate the safety of and the body's immune response to experimental HIV vaccine regimens using different vaccine priming combination, and boosting with the vaccines NYVAC and AIDSVAX® B/E.

开始日期2012-08-01

申办/合作机构

HIV Vaccine Trials Network

100 项与 HIV DNA vaccine(GENEART AG) 相关的临床结果

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100 项与 HIV DNA vaccine(GENEART AG) 相关的转化医学

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100 项与 HIV DNA vaccine(GENEART AG) 相关的专利（医药）

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项与 HIV DNA vaccine(GENEART AG) 相关的文献（医药）

2022-07-29·Science Immunology

A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques

Article

作者: Jones, Andrew T. ; Clements, John D. ; Shiferaw, Ayalnesh ; Qin, Zhaohui S. ; Ward, Andrew B. ; Amara, Rama Rao ; Cheedarla, Narayanaiah ; Derdeyn, Cynthia A. ; Yi, Lasanajak ; Lee, Wen-Hsin ; Shen, Xiaoying ; Alter, Galit ; Burton, Samantha ; Ozorowski, Gabriel ; Walter, Korey L. ; Styles, Tiffany M. ; Sahoo, Anusmita ; Williams, LaTonya D. ; Roy, Vicky ; Varadarajan, Raghavan ; Tomaras, Georgia D. ; Kozlowski, Pamela A. ; Song, Xuezheng ; Gangadhara, Sailaja

The rising global HIV-1 burden urgently requires vaccines capable of providing heterologous protection. Here, we developed a clade C HIV-1 vaccine consisting of priming with modified vaccinia Ankara (MVA) and boosting with cyclically permuted trimeric gp120 (CycP-gp120) protein, delivered either orally using a needle-free injector or through parenteral injection. We tested protective efficacy of the vaccine against intrarectal challenges with a pathogenic heterologous clade C SHIV infection in rhesus macaques. Both routes of vaccination induced a strong envelope-specific IgG in serum and rectal secretions directed against V1V2 scaffolds from a global panel of viruses with polyfunctional activities. Envelope-specific IgG showed lower fucosylation compared with total IgG at baseline, and most of the vaccine-induced proliferating blood CD4 + T cells did not express CCR5 and α4β7, markers associated with HIV target cells. After SHIV challenge, both routes of vaccination conferred significant and equivalent protection, with 40% of animals remaining uninfected at the end of six weekly repeated challenges with an estimated efficacy of 68% per exposure. Induction of envelope-specific IgG correlated positively with G1FB glycosylation, and G2S2F glycosylation correlated negatively with protection. Vaccine-induced TNF-α + IFN-γ + CD8 + T cells and TNF-α + CD4 + T cells expressing low levels of CCR5 in the rectum at prechallenge were associated with decreased risk of SHIV acquisition. These results demonstrate that the clade C MVA/CycP-gp120 vaccine provides heterologous protection against a tier2 SHIV rectal challenge by inducing a polyfunctional antibody response with distinct Fc glycosylation profile, as well as cytotoxic CD8 T cell response and CCR5-negative T helper response in the rectum.

2021-12-01·Trials4区 · 医学

Participants’ characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa

4区 · 医学

ArticleOA

作者: Nzuza, Ayanda ; Reddy, Tarylee ; Carpenter, Bradley ; Gaffoor, Zakir ; Hanass-Hancock, Jill ; Andrasik, Michele ; Goga, Ameena

AbstractBackgroundHIV is one of the greatest public health challenges in South Africa. Potential HIV vaccines and antibodies are thought to be cost-effective biomedical HIV prevention methods and are currently under investigation in phase I, II, and III trials. Consequently, current and future clinical trials need to ensure sufficient recruitment and retention. To achieve this goal, clinical trial staff need to understand the socio-demographic and behavioural characteristics of people volunteering to screen for these trials and their reasons for volunteering.MethodsWe conducted a secondary analysis of participant screening data across five vaccine and monoclonal antibody trials at four sites in KwaZulu-Natal, South Africa. Our study reviewed the demographic, behavioural, motivational, and health-related data from the case report forms and screening questionnaires. Descriptive statistics, chi-squared, and one-way ANOVA tests were used to analyse participants’ characteristics and motivation to participate in HIV vaccine and monoclonal antibody trials. Analyses were conducted using R version 3.5.2.ResultsScreening data from 1934 participants, including 79.2% of women, were obtained across all five trials (1034 enrolled, 900 screened out/declined). Screened participants predominately self-identified as black, heterosexual, cisgender women or men, many with lower educational backgrounds (43.9% did not complete secondary/high school), and several self-reported HIV-risk behaviours among themselves and their partners. 10.8% of the screened participants were living with HIV. Avoiding HIV risk was the main motivation to participate in clinical trials, followed by altruistic reasons such as a desire to help the community or helping to find a vaccine.DiscussionThe current recruitment approach of these trials attracts heterosexual participants who seek to reduce HIV risk and support their community. Hence, the data suggest the need for and potential acceptance of continued ongoing HIV prevention efforts. Current trials attract participants with lower educational levels, which may be driven by the site locations, current community mobilisation strategies and research site opening hours. The sites could consider more flexible working hours to accommodate working participants and find ways to connect participants to educational support and opportunities to upgrade education levels for the current clientele.Trial registrationHVTN 100: A Safety and Immune Response Study of 2 Experimental HIV Vaccines, NCT02404311. Registered on March 17, 2015.HVTN 111: Safety and Immune Response to a Clade C DNA HIV Vaccine, NCT02997969. Registered on December 16, 2016.HVTN 108: Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults, NCT02915016. Registered on September 22, 2016.HVTN 702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa, NCT02968849. Registered on November 1, 2016.HVTN 703/HPTN 081: Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women, NCT02568215. Registered on October 1, 2015.

2019-09-30·Journal of Clinical Investigation1区 · 医学

DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial

1区 · 医学

Article

作者: Rouphael, Nadine G ; Jensen, Ryan ; Li, Shuying S ; Montefiori, David C ; Pantaleo, Giuseppe ; Wilson, Gregory J ; Norwood, Aliza ; Sinangil, Faruk ; De Rosa, Stephen C ; Karuna, Shelly ; Morgan, Cecilia ; Sanchez, Brittany ; Ferrari, Guido ; Swann, Edith ; Maenza, Janine ; Tomaras, Georgia D ; Tieu, Hong-Van ; Sobieszczyk, Magdalena E ; Kobie, James ; Frank, Ian ; Keefer, Michael C ; McElrath, M Juliana ; Ding, Song

BACKGROUNDRV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein).METHODSOne hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit.RESULTSAll regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%-100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%-100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. CD4+ T cell responses were detectable in all treatment groups (32%-64%) without appreciable CD8+ T cell responses.CONCLUSIONThe DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2-binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses.TRIAL REGISTRATIONClinicalTrials.gov NCT02207920.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845).

100 项与 HIV DNA vaccine(GENEART AG) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
获得性免疫缺陷综合征	临床2期	乌干达	EuroVacc Foundation	2014-09-01
曼氏血吸虫病	临床2期	乌干达	EuroVacc Foundation	2014-09-01
HIV感染	临床2期	-	GENEART AG	-
HIV感染	临床2期	-	EuroVacc Foundation	-
HIV感染	临床2期	-	University of Regensburg	-