Network Immunology now has experimental evidence in both mice and humans that supports its HIV vaccine concept. The evidence in mice is a recently discovered phenomenon called “MHC restriction of V-V interactions in serum IgG”, documented by Network Immunology scientists Geoffrey Hoffmann and Earnest Leung. The evidence in humans is a surprising phenomenon published by Donald Tankersley, Sue Preston and J. S. Finlayson of the Office of Biologics Research and Review, Division of Blood Products in Bethesda, Maryland, that has recently been interpreted in terms of immune network theory and supports the Network Immunology HIV vaccine concept.

The Network Immunology team is continuing its pre-clinical studies in order to gain additional experimental support, but Dr. Hoffmann says there is little more actual ’development’ to be done.  “We are confident we now know what the essential vaccine components are,” he stated in a recent meeting.

A New Approach to an HIV Vaccine:

The Network Immunology vaccine, HOFFIVAC™ consists of a diverse mixture of proteins that resemble HIV in a key way. This mixture is expected to trigger an immune response that includes antibodies against multiple forms of HIV, even though the vaccine does not contain HIV or any components of HIV. The immune response to this mixture is expected to provide full protection against HIV infection.

A Company with a Unique Focus:

Network Immunology Inc. has unique expertise in immune network theory. Immune network theory is based on Nobel laureate Niels Jerne’s immune network hypothesis and has been developed in detail by Network Immunology’s Chief Scientist, Dr. Geoffrey Hoffmann, from the time when Hoffmann was a member of the Basel Institute for Immunology where Jerne was the Director. To our knowledge, no other company is developing technologies based specifically on immune network theory. For an in depth understanding of the underlying theoretical and experimental work that led to Network Immunology’s HIV vaccine concept, see Dr. Hoffmann’s UBC homepage for a list of his publications and a link to his recently published book on Immune Network Theory.

External Background on Immune Network Theory:

For background on this network theory of the immune system, see Wikipedia’s Immune Network Theory page.

Dr. Geoffrey Hoffmann published a book online entitled “Immune Network Theory”.

See Dr. Hoffmann’s UBC homepage for a link to this book.

The Network Immunology vaccine consists of a diverse reagent that is not HIV or part of HIV, but which resembles the diversity of HIV in an important way. Immunization with this reagent is expected to result in the production of antibodies that bind to many versions of HIV. This is the first mode of action of the vaccine. The vaccine also has a second mode of action. HIV infects a diverse population of cells called helper T cells. The Network Immunology approach involves vaccinations that are designed to change the helper T cells in a way that makes them less susceptible to infection by HIV, without otherwise compromising their function.

There are molecules in the immune system called MHC class II, that play a very important role by the way they interact with a set of white blood cells called helper T cells. The helper T cells are very diverse, and each helper T cell has a set of molecules on its surface called T cell receptors. These T cell receptors have “variable regions” that are very diverse shapes, but the shapes are not completely random. Only those helper T cells are selected that have T cell receptors with affinity for the MHC class II molecules.

Another important set of cells that regulate immune responses are suppressor T cells, that interact with the helper T cells. In the network theory the suppressor T cells are selected such that each of them interacts with as many helper T cells as possible. At the same time the helper T cells are selected on the basis of their receptors having shapes that are complementary not only to MHC class II, but also to the receptors of the suppressor T cell population. The resulting mutually stabilizing relationship between the helper T cells and the suppressor T cells is similar to the canvas and the centre-pole of a tent. The centre-pole holds up the canvas, and the canvas holds up the centre-pole.

HIV preferentially infects those helper T cells that have T cell receptors that bind HIV. This aspect of HIV pathogenesis was postulated in a paper on immune network theory in 1994. See “Co-selection in immune network theory and in AIDS pathogenesis” by G. W. Hoffmann, Immunology and Cell Biology (1994) 72, 338-346. Eight years later this postulate was validated; see “HIV preferentially infects HIV-specific CD4+ T cells” by D. C. Douek et alia, Nature (2002) 417, 95-98. This means that the criterion for selection of HIV variants is the same as the criterion for the selection of the suppressor T cells. Consequently with time the selected HIV variants resemble the V regions of the suppressor T cell population more and more. Then the immune response against HIV is directed also against this central regulating element of the immune system.

Network Immunology has obtained evidence that active ingredients in its HIV vaccine have an important similarity to the central regulating element. At the same time the vaccine is a diverse reagent, and recent developments in the network theory of adaptive immunity lead to the prediction that the immune response to the vaccine will prevent against infection by a wide range of HIV variants.