Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults.

Two double-blind randomised controlled studies (phase I and I/II) were performed to assess for the first time the safety and immunogenicity of a recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine in 148 healthy adult volunteers. All candidate vaccine formulations had a good safety profile and were well tolerated, with the incidence of solicited and unsolicited symptoms within a clinically acceptable range. One serious adverse event was reported in the phase I trial which was considered to be of suspected relationship to vaccination. The gp350 vaccine formulations were immunogenic and induced gp350-specific antibody responses (including neutralising antibodies).

Potency assay design for adjuvanted recombinant proteins as malaria vaccines.

Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modern vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development.

Industrial implementation of in vitro production of monoclonal antibodies.

Monoclonal antibodies are widely used at GlaxoSmithKline Biologicals (GSK Bio) for the quantification and characterization of antigens and for the release of vaccine lots. In 1998, GSK Bio decided to change the production of monoclonal antibodies (MAbs) designed for immunological tools from in vivo to in vitro technology. In 2004, all MAbs used at GSK Bio were produced in vitro. These MAbs cover more than 100 different targets with a variety of 1500 hybridomas, and approximately 60 to 90 MAbs are produced every year. This article describes the development process, including a description of the different systems tested based on double membrane or hollow fiber technology. The productivity, assets, and drawbacks of the different technologies are presented, and evaluation strategies for the choice of in vitro systems are discussed. Binding kinetics displayed by MAbs produced in vitro and in vivo were found to be similar, and MAbs produced in vitro are suitable tools for various immunological applications.