Smallpox resistance

Preventive medicine through vaccination continues to be the most cost-effective pubHc health practice, even with the drastic advance in modern medicine. Mass vaccination programs have eradicated smallpox from the earth. The World Health Organization (WHO) has a major campaign underway to eradicate poHo by the year 2000. The development of vaccines has saved millions of Hves and prevented many more from suffering. However, there are stiU many diseases without effective vaccines, such as malaria. With the recent emergence of antibiotic-resistance strains and exotic vimses, an effective vaccine development program becomes a top priority of pubHc health poHcy. 

Vaccinia An infection, primarily local and limited to the site of inoculation, induced in man by inoculation with the vaccinia (coxpox) virus in order to confer resistance to smallpox (variola). On about the third day after vaccination, papules form at the site of inoculation which become transformed into umbilicated vesicles and later pustules they then dry up, and the scab falls off on about the twenty-first day, leaving a pitted scar in some cases there are more or less marked constitutional disturbances. 

Smallpox—Virus infection that causes fever and skin eruptions, frequently fatal. Smallpox has been eradicated by worldwide campaigns to vaccinate, making the body s immune system able to resist infection by the introduction beneath the skin of a small amount of a harmless form of the virus. 

Three basic approaches are used to control viral diseases vaccination, antiviral chemotherapy, and stimulation of host resistance mechanisms. Vaccination has been used successfully to prevent measles, rubella, mumps, poliomyelitis, yellow fever, smallpox, chickenpox, and hepatitis B. Unfortunately, the usefulness of vaccines appears to be limited when many stereotypes are involved (e.g., rhinoviruses, HIV). Furthermore, vaccines have little or no use once the infection has been established because they cannot prevent the spread of active infections within the host. Passive immunization with human immune globulin, equine antiserum, or antiserum from vaccinated humans can be used to assist the body s own defense mechanisms. Intramuscular preparations of immune globulin may be used to prevent infection following viral exposure and as replacement therapy in individuals with antibody deficiencies. Peak plasma concentrations of intramuscular immune globulins occur in about 2 days. In contrast, intravenously administered immune globulin provides immediate passive immunity. 

Jenner used pustular material from a cowpox lesion as an inoculum instead of similar material from a smallpox lesion. For this experiment, he inoculated cowpox lesion material from the hand of a milkmaid into the skin of an 8-year-old boy (Figure 1.1). The boy resisted variolation when challenged with smallpox about 6 weeks later. During another outbreak, several more inoculations were performed, and subsequent inoculations took place by arm-to-arm transfer of infectious material. Two years later, Jenner wrote The Inquiry (An inquiry into the causes and effects of the variolae vaccinae, a disease discovered in some of the Western countries of England, particularly Gloucestershire, and known by the name of Cow Pox). By 1799, Jenner s observations had been confirmed by several other practitioners, and over 1000 people had received the cowpox vaccine. Within another 3 years, the practice of cowpox inoculations had spread across Europe to North America and Asia, utilizing... 

Galvani AP, Slatkin M. Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele. Proc Natl Acad Sci USA 2003 100(25) 15276-15279. 

There are just a few studies of the use of caspase inhibitors to prevent apoptosis. Most studies concentrate on the expression of proteins of the IAP family (XIAP being the most noticeable) and the viral components p35 and CrmA (Vives et al., 2003a). CrmA, encoded by the smallpox virus, is a pseudo-substrate for serine and cysteine proteases. It inhibits caspases 1, 8, and 10 in several cell types (Sauerwald et al., 2003). p35 is a wide-spectrum caspase inhibitor encoded by baculoviruses, and it also behaves as a pseudo-substrate, inhibiting caspases 1, 3, 6, 7, 8, and 10 (Zhou et al., 1998). XIAP is the most potent member of the IAP family. It is found in the mammalian genome and is responsible for the inhibition of caspases 3, 7, and 9 (Sauerwald et al., 2002). An increased protective effect is found in CHO and HEK-293 cells expressing a XIAP mutant resistant to degradation (XIAP-BIR123) when compared with the wild-type protein (Sauerwald et al., 2002). 

How could I resist such an invitation I bought a pie like a true Londoner, took it down to the river, watched the mass of oars on the choppy water, and looked downstream to where Flora must be moored somewhere among a distant forest of masts. I remembered that Shales had once given a sermon about the river and how it was a link between his past and his present. No wonder his face in repose was full of sorrow, when he had lost his beloved wife so needlessly to smallpox. 

Stickl H, Helming M. Eitrige Meningitiden nach der Pockenschutzimpfung. [Purulent meningitides following smallpox vaccination. On the problem of post-vaccinal decrease of resistance.] Dtsch Med Wochenschr 1966 91(29) 1307-10. 

My attention to this singular disease (cowpox) was first excited by observing, that among those whom in the country I was called upon to inoculate, many resisted every effort to give them the smallpox. These patients I found had undergone a disease they called the cowpox. 

Genetic resistance to smallpox lessons from mousepox... 

We have used the mousepox model as a model for smallpox to imderstand the roles and mechanisms of some host and viral genes in conferring resistance to disease and show that both viral and host genes profoimdly influence the outcome of infection. 

Early attempts to control smallpox included inoculation with material from smallpox lesions. This practice, known as variolization, caused severe cases of smallpox in about 1 in 200 inoculations.84 In 1796, Jenner noted that milkmaids were free of the facial scars that marked most of the population during the smallpox epidemics of that time. The observation that they cannot take smallpox was attributed to the localized pox lesions that they developed on their hands. Jenner reasoned that infectious material (which he dubbed a virus ) from cowpox lesions provided protection from smallpox, and used it to vaccinate an 8-year-old boy. The boy later resisted variolation, demonstrating that an animal poxvirus that is not virulent for humans could be used as a potent vaccine against smallpox.85... 

Russian scientists may have continued work on this virus. This includes the introduction of Ebola and VEE genes into smallpox to create a whole new kind of BW agent, a so-called chimera virus. This would not only resist vaccine or anti-viral treatments, but also have a synergistic effect. In the late 1980s, a strain of a combined ectromelia (mousepox, a close relative of smallpox) and VEE genes created symptoms of both diseases in laboratory animals. Ken Alibek is convinced that this BW-related research work still continues in Russia, despite Yeltsin s decree banning all such activity. ... 

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