HIV Vaccine Research
Statens Serum Institut (SSI) is doing research in immunity against virus using especially HIV-1 (a chronic virus) and pandemic influenza A (an acute virus) as models relevant for public health.
The purpose is to help understand the protective immunity induced during virus infections and during vaccinations using different vaccine principles and modalities. We are contributing to the development of new innovative vaccine principles against these model virus diseases and similar virus diseases.
SSI also develops novel molecular biology methods for diagnosis and genotyping of all human disease related virus, especially emerging and bio-terror related virus.
With more than 40 million HIV infected individuals in the world (most of which are in Africa) this pandemic is out of control and there is a great need for development of therapeutic and prophylactic vaccines. The HIV infection does not leave life-long immunity but leads to break-down of the immune system, opportunistic infections and death. If left untreated, the patient’s immune system can only partly control the infection. The purpose of vaccination is therefore to induce a broader, stronger and more rationally directed immunity than the one induced by the natural infection. Even though patients in Denmark are offered anti-retroviral medicine (ART) when the patient’s CD4 count drops below 200-300/microliter, the medication does have unwanted side effects and problems. When ART starts it is daily and life long. Thus there is a need for new rational vaccines and therapies that may help controlling the virus and prolong the period until ART or AIDS.
HIV-1 cellular immunity
This project aims at introducing a new treatment principle for individuals with chronic HIV-1 infection not yet in ART. We have used synthetic peptides representing CTL epitopes for immunizing patients having the tissue type HLA-A2. We used the patients own monocyte derived dendritic cells as “natural” adjuvants. Preliminary data show no side effects and shows that novel immunity can be induced to the subdominant CD8 and CD4 epitopes we have identified. Thus, next step is to broaden and improve this immune induction using more epitope peptides representing conserved epitopes restricted to most HLA A and B types worldwide. For this, we use a new adjuvant, CAF, developed at SSI which supports the type of immunity we anticipate. At the same time, we examine the cellular immunity that the HIV-1 infection induced in different categories of HIV controllers to use this for improving immunization principles. We continue our immunogen discovery program to identify new and improved targets and immunogens that will inhibit HIV-1 replication in cells. Such “vaccines” have both therapeutic and prophylactic potentials and has been recently tested clinically in Denmark and West Africa supported by grants from DANIDA, EDCTP and AIDS Fondet DK.
SSI are collecting and characterizing envelopes from Denmark and West Africa from patients having themselves broadly neutralizing antibodies. Suitable envelopes are then synthesized as genes optimized for expression of trimerised molecules when used as 2nd generation DNA vaccines and/or purified proteins. We use several animal models for the testing, e.g. mice, guinea pigs, rabbits and monkeys. Our most promising candidate so far is tested successfully in monkeys in France an EU collaboration (NGIN EU7FP). The promising results will result in a therapeutic vaccine component for antibody induction and be combined with the optimized vaccine component inducing protective cellular immunity.