Journal of IiME Volume 8 Issue 1 May 2014 Human Enteroviruses and Type 1 Diabetes Can a vaccine be created against enteroviruses which will eliminate T1D and perhaps all other enteroviral diseases as well? Good question. Vaccines usually target at most a few viruses; the polio vaccines targeted three types of poliovirus, for example. A major developmental problem for T1D is that at present, we do not know which enteroviruses cause T1D: there are at least 100 known and many more uncharacterized human enteroviruses. This is far too many to target for a vaccine, especially if some or many play no role in the disease. For a classical vaccine approach to be considered, we must determine which enteroviruses cause T1D, and determine how the viruses cause the disease. That enteroviruses in species B are likely the key players, suggests the relevant field has been winnowed significantly already. Research on this topic should be actively encouraged. Of course, there is also the question of how many cases of T1D are indeed caused by enteroviral infections. If enteroviruses do not cause many cases, no company would ever make a vaccine because the market would be so small. That is a hard fact: cures are dependent upon the free market. We know that CVB and other species B enteroviruses are involved in T1D induction. However, work is required to identify the viruses that are found in the pancreas tissue of diabetic humans. That said, we have been speaking so far about a classical vaccine: one which develops protective antiviral immunity against specific virus(es) serotypes that protects one against disease caused by subsequent exposure to the same virus(es) serotypes. There are potentially other approaches to vaccination, ones which may not involve the generation of protective immunity but instead, a generic or pan-enterovirus immunity. The possibility exists that one can induce the immune system to recognize enteroviruses in general, such that when it comes up against an actual virus infection, the immune response will be much more rapid. That may be all that is required and that would be rather readily accomplished. Such an approach is not a "silver bullet" like, for example, the polio vaccines; such an approach would offer a much better chance at suppressing a potentially T1D-causing infection but might protect all people. This, too, is worthy of research support because of its immense potential, not only for T1D but for viral diseases in general. In fact, we now have a large amount of data demonstrating that we can actually vaccinate NOD mice in this way and protect them not only from their own autoimmune T1D but also from CVB-induced T1D later in life. Therefore, we believe that the potential for this approach is huge. In one scenario, using standard and wellunderstood (from the poliovirus vaccine experience) technologies, a safe, protective antienteroviral vaccine could be devised. While it would not completely protect the individual from virus disease in the same manner that the polio vaccines prevent poliomyelitis, such an approach could slow the infection sufficiently so that the immune response would have a vital few extra days to respond and clear the infection. Again, data from the mouse model indicates this slowing of new infections is tightly linked to lowering the chance of developing virus-induced T1D. The goal should always be to eradicate the disease, while an acceptable compromise is to greatly reduce the incidence of the disease. To focus primarily on treating people with the disease is unacceptable. 7. The importance of basic research to help find the cure to T1D. That which we understand about human enteroviruses and their impact upon T1D development has been derived from basic research. As scientists and citizens, we are driven by the need for a cure, but we must temper our approach as we know that if we chase off down a promising but blind alley, we will waste valuable time. Ignoring basic research while emphasizing only clinical palliative efforts will never eradicate or suppress the disease. The goal should always be to eradicate the disease, while an acceptable compromise is to greatly reduce the incidence of the disease. To focus primarily on treating people with the disease is unacceptable. 1. Tracy et al. 2002 J Virology 76:12097-12111 2. Drescher et al. 2004 Virology 329: 381-394 Invest in ME (Charity Nr. 1114035) www.investinme.org Page 33 of 52

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