Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women.

Background: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence.

Comparison of Antibody Responses Induced by RV144, VAX003, and VAX004 Vaccination Regimens.

The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens, and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and Cyclic V2 (CycV2) and CycV3 peptides and gp70 V1 V2 scaffolds in these 3 HIV vaccine trials.

Challenges and successes for the grantees and the Technical Advisory Group of WHO's influenza vaccine technology transfer initiative.

One of the aims of the WHO Global Action Plan for Influenza Vaccines (GAP) was to transfer influenza vaccine production technology to interested manufacturers and governments in developing countries, to enable greater influenza vaccine manufacturing capacity against any pandemic threat or pandemic. For this objective, the GAP was supported by an independent Technical Advisory Group (TAG) to assist WHO to select vaccine manufacturing proposals for funding and to provide programmatic support for successful grantees. While there were many challenges, for both the TAG and grantees, there were also notable successes with an additional capacity of 338-600 million pandemic vaccine doses being made possible by the programme between 2007 and 2015, and a potential capacity of more than 600 million by 2016/17 with up to one billion doses expected by 2018/19.

IgG Antibody Responses to Recombinant gp120 Proteins, gp70V1/V2 Scaffolds, and a CyclicV2 Peptide in Thai Phase I/II Vaccine Trials Using Different Vaccine Regimens.

RV144 correlates of risk analysis showed that IgG antibodies to gp70V1V2 scaffolds inversely correlated with risk of HIV acquisition. We investigated IgG antibody responses in RV135 and RV132, two ALVAC-HIV prime-boost vaccine trials conducted in Thailand prior to RV144. Both trials used ALVAC-HIV (vCP1521) at 0, 1, 3, and 6 months and HIV-1 gp120MNgD and gp120A244gD in alum (RV135) or gp120SF2 and gp120CM235 in MF59 (RV132) at 3 and 6 months.

Global vaccine supply. The increasing role of manufacturers from middle income countries.

Hallmarks in the remarkable evolution of vaccines and their application include the eradication of smallpox, the development and delivery of the early childhood vaccines and the emergence of recombinant vaccines initiated by the hepatitis B vaccine. Now we enter a most exciting era as vaccines are increasingly produced and delivered in less developed countries. The results are dramatic decreases in childhood morbidity and mortality around the world.

Deadly AIDS policy failure by the highest levels of the US government: a personal look back 30 years later for lessons to respond better to future epidemics.

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.

Safety and reactogenicity of canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E vaccination in an efficacy trial in Thailand.

Background: A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand.

Methodology/principal Findings: Reactogenicity was recorded for 3 days following vaccination.

Safe landing for global polio eradication: a perspective.

After over two decades of immense efforts, the global polio eradication initiative may be approaching its final phase. With leadership from WHO, great efforts of national programs and support from its collaborators, combined with the recent use of mono and bivalent oral polio vaccines, success may be at hand. For a "safe landing" of this global program, it is important once more to recall the key role of routine vaccination as the foundation on which mass vaccination campaigns can be successful.

WHO influenza vaccine technology transfer initiative: role and activities of the Technical Advisory Group.

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.

Dengue vaccines regulatory pathways: a report on two meetings with regulators of developing countries.

Richard Mahoney and colleagues summarize two recent meetings convened by the Pediatric Dengue Vaccine Initiative and the Developing Countries' Vaccine Regulators Network on regulatory issues that need to be addressed before licensing dengue vaccines.

Successes and failures: Worldwide vaccine development and application.

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.

Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.

Background: The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control.

Methods: In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand.

HIV-1 virologic and immunologic progression and initiation of antiretroviral therapy among HIV-1-infected subjects in a trial of the efficacy of recombinant glycoprotein 120 vaccine.

The first trial of the efficacy of a human immunodeficiency virus (HIV)-1 vaccine was conducted in North America and The Netherlands between 1998 and 2003. This multicenter, randomized, placebo-controlled trial of a recombinant glycoprotein 120 vaccine included 5403 initially HIV-negative volunteers who were monitored for 3 years. The 368 subjects who acquired HIV-1 infection were monitored for 2 years by use of the following postinfection end points: plasma HIV-1 RNA level (viral load), CD4+ lymphocyte count, initiation of antiretroviral therapy (ART), and HIV-1-related clinical outcomes.

Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial.

Background: An objective of the first efficacy trial of a candidate vaccine containing recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein 120 (rgp120) antigens was to assess correlations between antibody responses to rgp120 and the incidence of HIV-1 infection.

Methods: Within the randomized trial (for vaccinees, n=3598; for placebo recipients, n=1805), binding and neutralizing antibody responses to rgp120 were quantitated. A case-cohort design was used to study correlations between antibody levels and HIV-1 incidence.

Phase I/II study of a candidate vaccine designed against the B and E subtypes of HIV-1.

A phase I/II trial of a candidate vaccine to prevent HIV infection was carried out in Bangkok, Thailand, testing AIDSVAX B/E (VaxGen, Inc., Brisbane, CA), a bivalent subunit vaccine prepared by combining recombinant gp120 from a subtype B virus (HIV-1MN) with gp120 from a subtype E virus (HIV-1A244) in alum adjuvant. The studies provide human data on the immunogenicity of various dose combination of non-subtype B vaccine antigens.

Recruitment, screening and characteristics of injection drug users participating in the AIDSVAX B/E HIV vaccine trial, Bangkok, Thailand.

Objectives: To describe recruitment, screening and baseline characteristics of injection drug users (IDU) participating in a phase III HIV vaccine (AIDSVAX B/E; VaxGen, USA) trial and to compare enrollment characteristics between trial participants and 1209 IDU from a 1995-1998 vaccine trial preparatory cohort for changes that might impact trial design assumptions.

Methods: Enrollment for both studies was conducted at Bangkok narcotic treatment clinics, where a standardized questionnaire was administered on demographics, risk behavior and incarceration history over the previous 6 months.

Results: During 1999-2000, 4943 IDU were screened for enrollment; successful sources of recruitment included clinic attendees (43.

Medicine. The need for a global HIV vaccine enterprise.

A new collaborative model of research is needed to increase resources, to prioritize the R (ii) to increase the pace, reduce the overlap, and more systematically explore the elements of and delivery systems for vaccines; (iii) to use common standards for the prompt comparative testing of vaccine candidates; (iv) to expand resources for manufacturing vaccine candidates to speed their use in human trials; and (v) to increase the capacity for international clinical trials and to focus this effort toward quickly measuring the effectiveness of vaccine protection as prototype vaccine candidates are identified.