Global Solutions for Infectious Diseases

South San Francisco, CA, United States

Global Solutions for Infectious Diseases

South San Francisco, CA, United States
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Francis D.P.,Global Solutions for Infectious Diseases | Grohmann G.,Therapeutic Goods Administration
Vaccine | Year: 2011

In May 2006, the WHO published a Global Pandemic Influenza Action Plan. A significant part of that plan involves the transfer of technology necessary to build production capacity in developing countries. The WHO influenza technology transfer initiative has been successful. Clearly the relatively small WHO investments made in these companies to develop their own influenza vaccine production facilities have had quite dramatic results. A few companies are already producing large amounts of influenza vaccine. Others will soon follow. Whether they are developing egg-based or planning non-egg based influenza vaccine production, all companies are optimistic that their efforts will come to fruition. © 2011 Elsevier Ltd.

Perez-Losada M.,University of Porto | Jobes D.V.,Jobes Consulting Service | Sinangil F.,Global Solutions for Infectious Diseases | Crandall K.A.,Brigham Young University | And 3 more authors.
PLoS ONE | Year: 2011

Background: In 2003, a phase III placebo-controlled trial (VAX003) was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU), we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120) from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand. Methodology and Findings: Phylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL) and CD4+ counts, to indentify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections), subtype B (13%) and CRF15_AE (2%). The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02) in genetic diversity were observed in CRF01_AE IDU with different VL and CD4+ counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50%) of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983-1986), 3-6 years before the first recognition of symptomatic patients (1989). The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s. Conclusions: Our study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid AIDS resurgence. © 2011 Pérez-Losada et al.

Chung A.W.,Massachusetts General Hospital | Ghebremichael M.,Massachusetts General Hospital | Robinson H.,Massachusetts General Hospital | Brown E.,Dartmouth College | And 21 more authors.
Science Translational Medicine | Year: 2014

The human phase 2B RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial, held in Thailand, resulted in an estimated 31.2% efficacy against HIV infection. By contrast, vaccination with VAX003 (consisting of only AIDSVAX B/E) was not protective. Because protection within RV144 was observed in the absence of neutralizing antibody activity or cytotoxic T cell responses, we speculated that the specificity or qualitative differences in Fc-effector profiles of nonneutralizing antibodies may have accounted for the efficacy differences observed between the two trials. We show that the RV144 regimen elicited nonneutralizing antibodies with highly coordinated Fc-mediated effector responses through the selective induction of highly functional immunoglobulin G3 (IgG3). By contrast, VAX003 elicited monofunctional antibody responses influenced by IgG4 selection, which was promoted by repeated AIDSVAX B/E protein boosts. Moreover, only RV144 induced IgG1 and IgG3 antibodies targeting the crown of the HIV envelope V2 loop, albeit with limited coverage of breakthrough viral sequences. These data suggest that subclass selection differences associated with coordinated humoral functional responses targeting strain-specific protective V2 loop epitopes may underlie differences in vaccine efficacy observed between these two vaccine trials.

Sanofi S.A., U.S. Army, Global Solutions For Infectious Diseases and Ministry Of Public Health | Date: 2016-02-24

The disclosure relates to immunological compositions for vaccinating human beings against infection by the Human Immunodeficiency Virus (HIV).

Perez-Losada M.,University of Porto | Jobes D.V.,Presidio Pharmaceuticals Inc. | Sinangil F.,Global Solutions for Infectious Diseases | Crandall K.A.,Brigham Young University | And 2 more authors.
Molecular Biology and Evolution | Year: 2010

In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P=0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B was 1966-1970. Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.

Successful control of any dangerous epidemic requires: (i) early understanding of the epidemiology of the disease and (ii) rapid applications of preventive interventions. Through the lack of both policy and financial support, the United States Centers for Disease Control (CDC) was severely handicapped during the early years of the AIDS epidemic. Senior staff of the Reagan Administration did not understand the essential role of Government in disease prevention. Although CDC clearly documented the dangers of HIV and AIDS early in the epidemic, refusal by the White House to deliver prevention programs then certainly allowed HIV to become more widely seeded. As much of the international health community relies on CDC for up-to-date prevention advice, these actions by the White House surely increased the spread of HIV around the world. To respond better to future epidemics, we need to understand the deadly forces that inhibited CDC at that time. © 2012 Macmillan Publishers Ltd.

O'Rourke S.M.,University of California at Santa Cruz | Schweighardt B.,Monogram Biosciences | Phung P.,Monogram Biosciences | Fonseca D.P.A.J.,University of California at Santa Cruz | And 4 more authors.
Journal of Virology | Year: 2010

Understanding the determinants of neutralization sensitivity and resistance is important for the development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine. In these studies, we have made use of the swarm of closely related envelope protein variants (quasispecies) from an extremely neutralization-resistant clinical isolate in order to identify mutations that conferred neutralization sensitivity to antibodies in sera from HIV-1-infected individuals. Here, we describe a virus with a rare mutation at position 179 in the V2 domain of gp120, where replacement of aspartic acid (D) by asparagine (N) converts a virus that is highly resistant to neutralization by multiple polyclonal and monoclonal antibodies, as well as antiviral entry inhibitors, to one that is sensitive to neutralization. Although the V2 domain sequence is highly variable, D at position 179 is highly conserved in HIV-1 and simian immunodeficiency virus (SIV) and is located within the LDI/V recognition motif of the recently described α4β7 receptor binding site. Our results suggest that the D179N mutation induces a conformational change that exposes epitopes in both the gp120 and the gp41 portions of the envelope protein, such as the CD4 binding site and the MPER, that are normally concealed by conformational masking. Our results suggest that D179 plays a central role in maintaining the conformation and infectivity of HIV-1 as well as mediating binding to α4β7. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Francis D.P.,Global Solutions for Infectious Diseases
Biologicals | Year: 2010

The impact that vaccines have had on world health has been great. The misery prevented and the lives saved have been impressive. But all has not been good. As one looks at the success, one can also see the missed opportunities. This discussion takes a broad, worldwide view of vaccines - from early research, through development and application. It examines our successes and our failures and looks with great optimism towards a future having great potential to prevent much of today's suffering from infectious diseases. © 2010 The International Association for Biologicals.

Global Solutions For Infectious Diseases | Date: 2013-01-22

Vaccines; pharmaceutical preparations for the treatment and prevention of infectious diseases. Computer software for use in reading, digitizing, and transmitting point of care diagnostic test results for infectious diseases; computer software for use in capturing, storing, transmitting, and reporting point of care diagnostic test data including the test used, result, time, date, location, and demographic information; computer software for use in providing standardized interpretation of diagnostic test results and patient care guidelines to clinicians and community health workers; computer software to facilitate patient care, health-system evaluation, and global disease surveillance and control efforts; computer software for use by public health officials to access, aggregate, monitor, and analyze medical diagnostic data and to prepare customized reports; computer software for use by public health officials to gather, assess, and respond to real-time disease occurrence to improve disease control, detect disease outbreaks, and identify new and emerging disease threats.

Global Solutions For Infectious Diseases | Date: 2013-01-22

Vaccines; pharmaceutical preparations for the treatment and prevention of infectious diseases.

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