1. Introduction: Integrated Research Strategies

More than three decades following the description of isolated cases of an acquired immunodeficiency by the Center of Disease Control (CDC), the AIDS pandemic is continuously escalating despite excessive education campains. Still, the complex biology of the Human Immunodeficiency Virus is limiting the development of novel therapeutics and effective vaccines. Besides several pathogenicity factors, a series of immune escape mechanisms together with the extreme variability of retroviruses account for the occurrence of escape mutants, which defy from the control of both per se effective therapeutics and various effectors of the immune system.


Grafik Vaccines Strategies
Grafik Vaccines Strategies

Recent clinical experience from the treatment of viral (HIV) or bacterial (e.g. Mycobacteria) infections clearly suggests that the treatment success correlates with the number and combination of administered drugs. The principle of targeting different structures/steps of viral replication simultaneously holds true both for the design of therapeutic strategies as well as for the development of HIV candidate vaccines. In the case of HIV, recent considerations to design novel therapeutics not only include additional viral targets such as the group specific antigen (Gag), but rather extend to cellular ligands of viral proteins, which can not easily escape control by acquiring distinct mutations mediating drug resistancy. Accordingly, careful characterization of the molecular mechanisms underlying HIV replication is necessarily required in order to identify novel and ideally also cellular targets for therapeutic intervention.

In view of the ever increasing number of >15000 new infections per day, the availability of preventive and therapeutic vaccines is thought to be of ample importance to limit further spread of the epidemic especially in developing countries. Conventional and empirical vaccination strategies relying on (i) inactivated virus preparations, (ii) attenuated life vaccines, (iii) split vaccines or (iv) recombinant envelope preparations failed either due to the lack of efficacy or severe safety concerns. As a consequence, integrated vaccine strategies may be required to pave the way to a more rational vaccine design.

HIV Infections Worldwide - 2003
HIV Infections Worldwide - 2003

Accordingly, recent efforts of our group covered various fields studying the virus (i) in the population to select a representative virus strain as template for immunogen design, (ii) in HIV infected individuals to identify potential immune correlates of protection and (iii) in its target cells to get deeper insight into distinct molecular mechanisms of viral replication. These insights should translate into a rational immunogen design, improved gene delivery systems and optimized adjuvant strategies. Candidate vaccine preparations need stepwise testing in increasingly complex and instructive animal models, and shall feed - following GMP production and toxicological analysis - into phase 1 clinical trials.

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