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Kamali A.,Medical Research Council Uganda Virus Research Institute | Kamali A.,Uganda Virus Research Institute UVRI | Price M.A.,International AIDS Vaccine Initiative IAVI | Price M.A.,University of California at San Francisco | And 51 more authors.
PLoS ONE | Year: 2015

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. © 2015 Kamali et al.


Omosa-Manyonyi G.,University of Nairobi | Mpendo J.,Uganda Virus Research Institute IAVI | Ruzagira E.,Medical Research Council MRC Uganda Virus Research Institute UVRI | Ruzagira E.,Research Unit on AIDS | And 24 more authors.
PLoS ONE | Year: 2015

Background: Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. Methods: In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. Results: The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. Conclusion: Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses. Trial Registration: ClinicalTrials.gov NCT01264445. © 2015 Omosa-Manyonyi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Amin M.N.,University of Maryland, Baltimore | Mclellan J.S.,National Institute of Allergy and Infectious Diseases | Huang W.,University of Maryland, Baltimore | Orwenyo J.,University of Maryland, Baltimore | And 5 more authors.
Nature Chemical Biology | Year: 2013

A new class of glycan-reactive HIV-neutralizing antibodies, including PG9 and PG16, has been recently discovered that seem to recognize previously uncharacterized glycopeptide epitopes on HIV-1 gp120. However, further characterization and reconstitution of the precise neutralizing epitopes are complicated by the heterogeneity of glycosylation. We report here the design, synthesis and antigenic evaluation of new cyclic V1V2 glycopeptides carrying defined N-linked glycans at the conserved glycosylation sites (Asn160 and Asn156 or Asn173) derived from gp120 of two HIV-1 isolates. Antibody binding studies confirmed the necessity of a Man 5 GlcNAc 2 glycan at Asn160 for recognition by PG9 and PG16 and further revealed a critical role of a sialylated N-glycan at the secondary site (Asn156 or Asn173) in the context of glycopeptides for antibody binding. In addition to defining the glycan specificities of PG9 and PG16, the identified synthetic glycopeptides provide a valuable template for HIV-1 vaccine design. © 2013 Nature America, Inc. All rights reserved.


Monaco D.C.,Emory University | Dilernia D.A.,Emory University | Fiore-Gartland A.,Fred Hutchinson Cancer Research Center | Yu T.,Emory University | And 15 more authors.
Journal of Experimental Medicine | Year: 2016

HIV-1 adapts to a new host through mutations that facilitate immune escape. Here, we evaluate the impact on viral control and disease progression of transmitted polymorphisms that were either preadapted to or nonassociated with the new host's HLA. In a cohort of 169 Zambian heterosexual transmission pairs, we found that almost one-third of possible HLA-linked target sites in the transmitted virus Gag protein are already adapted, and that this transmitted preadaptation significantly reduced early immune recognition of epitopes. Transmitted preadapted and nonassociated polymorphisms showed opposing effects on set-point VL and the balance between the two was significantly associated with higher set-point VLs in a multivariable model including other risk factors. Transmitted preadaptation was also significantly associated with faster CD4 decline (< 350 cells/μl) and this association was stronger after accounting for nonassociated polymorphisms, which were linked with slower CD4 decline. Overall, the relative ratio of the two classes of polymorphisms was found to be the major determinant of CD4 decline in a multivariable model including other risk factors. This study reveals that, even before an immune response is mounted in the new host, the balance of these opposing factors can significantly influence the outcome of HIV-1 infection. © 2016 Mónaco et al.


PubMed | Medical Research Council Uganda Virus Research Institute, University of Oxford, IAVI, Kenya AIDS Vaccine Institute Institute of Clinical Research and 10 more.
Type: Journal Article | Journal: PloS one | Year: 2015

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.


Industry veteran adds biotech innovation depth to Finn Partners' global reach and EU expertise in pharma and patient advocacy NEW YORK and PARIS, Nov. 10, 2016 /PRNewswire/ -- Finn Partners announced today the appointment of Mina Volovitch as Head of its Paris office and senior partner in the agency's Global Health Practice. Volovitch will be based in Paris and report to Chantal Bowman-Boyles, managing partner, leading Finn Partners Europe and Gil Bashe, managing partner, Global Health. Volovitch's more than 20 years' experience in health communications includes work with the globe's leading names in medicine and public health including bioMérieux, Bristol Myers-Squibb, Lilly, Novartis, Roche, Sanofi Pasteur, Transgene, the French Cancer Society, the National League Against Cancer (largest French patient group), the ANRS (National Agency for Research on Aids), the Mérieux Foundation and IAVI. "Our European offices are adding more and more health work encompassing biotechnology, patient advocacy and health technology assignments.  Mina's dual-role as head of our Paris office and senior member of the global health practice demonstrates how our agency values and growth attract exceptional talent," said Bowman-Boyles. "Mina is among the great health communicators with knowledge and experience engaging some of the most influential players in medical innovation, patient advocacy and public health across Europe," said Bashe. "Her collaborative approach is already strengthening the service and insight Finn Partners offers health clients around the globe.  Just as importantly, she lives the Finn Partners value of making a difference in the world through her professional and volunteer efforts." Volovitch began her career at Merck working in marketing, eventually becoming director of communications at MSD Paris. Following Merck, Volovitch joined the Mérieux Institute (the vaccine innovator that is today Sanofi Pasteur), where she served as director of communications. In 1987, she created Mynecom, a specialist healthcare communications agency. Her professional experience includes running national and global professional- and patient-communications programs; handling issues in pharmaceuticals and health products; and expertise across AIDS, biotech, cardiology, immunology, infectious disease, medical devices, oncology and vaccines. She is also a member of the National League Against Cancer communications working group. "I am energized and proud to join Finn Partners during this exciting time of growth for its global health practice and Paris office," said Volovitch.  "I share the agency's commitment to make a difference in the world, and the icing on the cake is building upon professional relationships with colleagues with whom I've worked in the past. Quite simply, I have deep trust and respect for Finn Partners management team in building one of the world's fastest growing PR and marketing communications agencies," she added. About Finn Partners, Inc. Finn Partners was launched in late 2011 to realize Peter Finn's vision to create a leading communications agency dedicated to shaping a bold new future in which innovation and partnership are strong brand drivers. Finn Partners specializes in the full spectrum of marketing and public relations services, including digital and social media. Practice areas include arts, consumer, CSR and social impact, education, financial services, health, technology and travel & lifestyle. Since its inception four years ago, Finn Partners has received six agency awards that are indicators of client and cultural leadership: "Best Midsize Agency" in 2015, "Best Agency to Work For" in 2013 and "Best New Agency" in 2012 from the Holmes Report and "Midsize PR Firm of the Year" in 2015 and "Top Places to Work in PR" in 2013 from PR News. Headquartered in New York City, the company has approximately 550 employees, with offices in Chicago, Detroit, Fort Lauderdale, Jerusalem, London, Los Angeles, Munich, Nashville, Paris, Portland, San Francisco and Washington D.C., and offers international capabilities through its own global network and PROI Worldwide. Find us at www.finnpartners.com and follow us on Twitter @finnpartners.


News Article | November 17, 2015
Site: www.biosciencetechnology.com

Scientists at The Scripps Research Institute (TSRI) have new weapons in the fight against HIV. Their new study, published today as the cover article of the November issue of Immunity, describes four prototype antibodies that target a specific weak spot on the virus. Guided by these antibodies, the researchers then mimicked the molecular structure of a protein on HIV when designing their own potential HIV vaccine candidate. “This study is an example of how we can learn from natural infection and translate that information into vaccine development,” said TSRI Research Associate Raiees Andrabi. “This is an important advance in the field of antibody-based HIV vaccine development.” Andrabi served as first author of the study, working in the lab of senior author TSRI Professor Dennis R. Burton, who is also scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI. The findings build on the success of several recent TSRI studies showing that, with prompting, the immune system can develop antibodies to neutralize many strains of HIV. In the new study, the researchers carried out a series of experiments involving virus modifications, protein and antibody engineering. They found that four antibodies targeted a single spot on HIV’s surface called the V2 apex. This was significant because the V2 apex could be recognized by these antibodies on about 90 percent of known HIV strains—and even related strains that infect other species. A vaccine targeting this region could protect against many forms of the virus. “This region helps stabilize the virus, so it’s an important area to target if you want to neutralize HIV,” said Andrabi. Investigating further, the researchers noticed that two of the four antibodies had an unusual feature that could prove important in vaccine design. The immune system usually begins its fight against infection by activating immune B cells that express “germline” forms of antibodies, on their surface, to bind invading pathogens. Germline antibodies rarely bind viruses very effectively themselves; instead, they are precursors for more developed antibodies, which mutate and hone their response to the invader. Yet in the new study, two of the antibodies did not need to mutate to bind with the V2 apex; instead, these antibodies used part of their basic germline structure, encoded by non-mutated genes. This means any patient with HIV should, in theory, have the ability to kick-start the right immune response. Unfortunately, the immune system seems to naturally produce only a small number of these HIV-neutralizing germline antibodies. To generate an immune response that would favor these antibodies, it was critical for the scientists to find the right proteins in HIV that the antibodies could recognize and bind to. In the new study, the researchers succeeded in mimicking a structure on HIV called the native HIV coat protein. This let them design proteins that do indeed bind well to the germline antibodies and hopefully start a useful immune response. The next step will be to test the vaccine candidates in animal models. HAVI-ID; Pascal Poignard of TSRI and IAVI; and Chung-Yi Wu and Chi-Huey Wong of the Genomics Research Center, Academia Sinica and TSRI. This study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD), the International AIDS Vaccine Initiative (IAVI) and the United States Agency for International Development (USAID).


Home > Press > Kymouse success in steps to developing HIV vaccine: Kymab, the Scripps Research Institute and International AIDS Vaccine Initiative collaboration improves discovery and testing of promising HIV vaccine strategies Abstract: A new approach to developing a human vaccine against HIV has been developed by researchers at Kymab, a UK therapeutic antibody platform Company, The Scripps Research Institute (TSRI) of San Diego, California, and the International AIDS Vaccine Initiative (IAVI). HIV is one of the most intransigent targets for vaccine development, and no effective vaccine has been developed in thirty years of global research. The research, which tested the first step in an approach to develop effective vaccines against the range of HIV variants existing worldwide, is published in Science on Thursday 8 September, 2016, and was supported by funding from the International AIDS Vaccine Initiative and the US National Institutes of Health. The results show that Kymouse, which is a mouse that has been modified to mimic human antibody responses, is an effective platform for discovering and testing possible vaccines and suggest ways in which testing of vaccine candidates can be improved. "We increasingly recognize that traditional vaccine strategies will not be successful against all viruses, especially not HIV," says Dennis Burton, chair of the TSRI Department of Immunology and Microbial Science and scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center (NAC) at TSRI and the National Institutes of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID). "Together with the Kymab team, we have taken a novel approach in which have induced human antibodies in Kymouse that are at the beginning of the pathway to protective antibodies and which is a huge boost to our mission to develop an HIV vaccine." The work is based on the observation that a fraction of people who become infected by HIV develop broadly neutralizing antibodies against diverse HIV strains. Such antibodies would be ideal to protect against or possibly treat HIV infection - if a vaccine could be made to elicit them. However, these antibodies originate from a limited number of precursor antibody-producing cells in the body and acquire their unusual and protective properties only during a long course of infection. Moreover, although these cells have been activated when immunizing certain biased animal models, this is the first time it has been achieved through immunization of an immune system, as in the Kymouse, that resembles the human. The researchers injected Kymouse strains with a nanoparticle formed of 60 copies of a small protein that mimics HIV and was designed to bind and stimulate the specific precursor cells for one class of broadly neutralizing antibody. They expected to find just one such precursor cell (among tens of millions of such cells) in each immunized mouse. The research team then looked to see whether or not the mice had mounted an antibody response to this injection. Given the combined challenges of a complex immunogen structure and the rarity of the right antibodies, an effective response against the HIV immunogen was elicited remarkably efficiently. "Our phenomenal results with the teams at TSRI and IAVI came from work at the boundaries of protein engineering, immunology and vaccine technology," explains Professor Allan Bradley, Chief Technical Officer at Kymab and Director Emeritus of the Wellcome Trust Sanger Institute, who developed the Kymouse platform. "Using Kymouse, we show how an advanced vaccine candidate can search out the one cell among tens of million antibody-producing cells and make it proliferate. "Kymouse can deliver antibody responses that we need to build effective HIV vaccines." The team validated their antibody response by sequencing genes from more than 10,000 cell samples, and showed that genes from responding mice had the expected sequence for precursors to broadly neutralizing antibodies against the HIV target. "It is a big step forward in this branch of HIV vaccine development," says William Schief, TSRI Professor and Director of Vaccine Design for the IAVI Neutralizing Antibody Center at TSRI, in whose lab the vaccine nanoparticle was developed. "We have the first proof of principle that this HIV vaccine strategy and our vaccine candidate can work in a human immune system and trigger the first step in the pathway to developing broadly neutralizing and protective antibodies against the virus. "It is the very sort of response we'd want to see as we test components of a future vaccine." HIV has proved an extremely difficult challenge in vaccine development. The new research shows that Kymouse can produce antibodies of the type that could evolve to confer protection, suggests ways in which the immunization regime can be improved and indicates that Kymab's technologies will support and accelerate the search for other, rarer and perhaps even more effective antibodies. "About 35 million people have died of HIV/AIDS and 36 million are currently infected. Although a vaccine is the most likely way to stem this loss, no successful vaccine has been found in more than thirty years of HIV research," says Professor Paul Kellam, Vice President of Infectious Diseases and Vaccines at Kymab. "This is a pressing need and these results show that our Kymouse technologies can serve a vital part in the search for effective vaccines that help to protect against this most challenging disease." "This dramatic proof of concept gives us hope we can find better broadly effective vaccines for HIV and, indeed, for other infections, using the human immune system to help guide us along the best path." Participating Centers Kymab Ltd, Babraham Research Campus, Cambridge, UK Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA About Don Powell Associates LTD About Kymab Kymab is a leading biopharmaceutical company focused on the discovery and development of fully human monoclonal antibody drugs using its proprietary Kymouse™ antibody platform. Kymouse™ has been designed to maximize the diversity of human antibodies produced in response to immunization with antigens. Selecting from a broad diversity of fully human antibodies assures the highest probability of finding that rare drug candidate with best-in-class characteristics. The Kymouse™ naturally matures these molecules to highly potent drugs obviating the need for further time-consuming modifications. Kymab is using the platform for its internal drug discovery programs and in partnership with pharmaceutical companies. Kymab commenced operations in 2010 and has raised over US$120m of equity financing which includes $90m Series B financing. It has an experienced management team with a successful track record in drug discovery and development and has numerous therapeutic antibody programs in immune-oncology, auto-immunity; hematology, infectious disease and other areas. www.kymab.com About The Scripps Research Institute The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academy of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu. About International Aids Vaccine Initiative (IAVI) The International AIDS Vaccine Initiative (IAVI) is a global not-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. Founded in 1996 and operational in 25 countries, IAVI and its network of collaborators research and develop vaccine candidates. IAVI was founded with the generous support of the Alfred P. Sloan Foundation, The Rockefeller Foundation, The Starr Foundation, and Until There's A Cure Foundation. Other major supporters include the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, The John D. Evans Foundation, The New York Community Trust, the James B. Pendleton Charitable Trust; the Governments of Canada, Denmark, India, Ireland, Japan, The Netherlands, Norway, Spain, Sweden, the United Kingdom, and the United States, the Basque Autonomous Government (Spain), the European Union as well as the National Institute of Allergy and Infectious Diseases and The City of New York, Economic Development Corporation; multilateral organizations such as The World Bank and The OPEC Fund for International Development; corporate donors including BD (Becton, Dickinson & Co.), Bristol-Myers Squibb, Continental Airlines, Google Inc., Pfizer Inc, and Thermo Fisher Scientific Inc.; leading AIDS charities such as Broadway Cares/Equity Fights AIDS; and many generous individuals from around the world. For more information, see www.iavi.org. Contacts: For Kymab Don Powell Don Powell Associates Ltd +44 (0)778 6858220 +44 (0)1223 515436 Mary Clark, Supriya Mathur and Hollie Vile Hume Brophy +44 (0)207 862 6390 For TSRI Madeline McCurry-Schmidt Science Writer The Scripps Research Institute Tel: 858-784-9254 Office of Communications The Scripps Research Institute Tel: +1 858-784-2666 Fax: +1 858-784-8118 For IAVI Arne Näveke Executive Director Advocacy, Policy, Communications International AIDS Vaccine Initiative (IAVI) +1.212.847.1055 (office) +1.646.623.47.85 (mobile) If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


Kopycinski J.,Imperial College London | Hayes P.,Imperial College London | Ashraf A.,Imperial College London | Cheeseman H.,Imperial College London | And 9 more authors.
PLoS ONE | Year: 2014

A correlation between in vivo and in vitro virus control mediated by CD8+ T-cell populations has been demonstrated by CD8 T-cell-mediated inhibition of HIV-1 and SIV replication in vitro in peripheral blood mononuclear cells (PBMCs) from infected humans and non-human primates (NHPs), respectively. Here, the breadth and specificity of T-cell responses induced following vaccination with replication-defective adenovirus serotype 35 (Ad35) vectors containing a fusion protein of Gag, reverse transcriptase (RT), Integrase (Int) and Nef (Ad35-GRIN) and Env (Ad35-ENV), derived from HIV-1 subtype A isolates, was assessed in 25 individuals. The vaccine induced responses to a median of 4 epitopes per vaccinee. We correlated the CD8 responses to conserved vs. variable regions with the ability to inhibit a panel of 7 HIV-1 isolates representing multiple clades in a virus inhibition assay (VIA). The results indicate that targeting immunodominant responses to highly conserved regions of the HIV-1 proteome may result in an increased ability to inhibit multiple clades of HIV-1 in vitro. The data further validate the use of the VIA to screen and select future HIV vaccine candidates. Moreover, our data suggest that future T cellfocused vaccine design should aim to induce immunodominant responses to highly conserved regions of the virus. © 2014 Kopycinski et al.


PubMed | Imperial College London, IAVI and University of Rochester
Type: Clinical Trial, Phase I | Journal: PloS one | Year: 2014

A correlation between in vivo and in vitro virus control mediated by CD8+ T-cell populations has been demonstrated by CD8 T-cell-mediated inhibition of HIV-1 and SIV replication in vitro in peripheral blood mononuclear cells (PBMCs) from infected humans and non-human primates (NHPs), respectively. Here, the breadth and specificity of T-cell responses induced following vaccination with replication-defective adenovirus serotype 35 (Ad35) vectors containing a fusion protein of Gag, reverse transcriptase (RT), Integrase (Int) and Nef (Ad35-GRIN) and Env (Ad35-ENV), derived from HIV-1 subtype A isolates, was assessed in 25 individuals. The vaccine induced responses to a median of 4 epitopes per vaccinee. We correlated the CD8 responses to conserved vs. variable regions with the ability to inhibit a panel of 7 HIV-1 isolates representing multiple clades in a virus inhibition assay (VIA). The results indicate that targeting immunodominant responses to highly conserved regions of the HIV-1 proteome may result in an increased ability to inhibit multiple clades of HIV-1 in vitro. The data further validate the use of the VIA to screen and select future HIV vaccine candidates. Moreover, our data suggest that future T cell-focused vaccine design should aim to induce immunodominant responses to highly conserved regions of the virus.

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