The Variola Virus

The Variola virus otherwise known as the Small pox is an enveloped protected DNA containing virus that causes severe illness. Small pox has a history dating back to prehistory times. It is believed to have appeared around 10,000 BC in northeast Africa. Evidence was suggested by medical examination of mummies ; their skin appeared have contain skin lesions resembling those ones that have had small pox. The infection of the variola virus seemed uncontainable during the prehistory times and even during known history dating back to the 18th century. The clearest record for the study of the virus dates back to the well -known Microbiologist Edward Jenner. Because the disease was almost 100% fatal there were scientist searching for ways to perhaps
cure or prevent the disease. Edward Jenner’s study of the variola virus began when he overheard a milk maid exclaim “I will never have small pox because I’ve had cow pox..”. This was the beginning of Jenner’s major conclusions. The milk maid’s expression would be a major factor contributing to the study and immunology of the disease. It is important to recognize that variola, cow pox, monkey pox, chicken and so on are different viruses, however the importance of cow pox is crucial to the eradication of the variola virus.
The immunology, however, is quite similar. The Centers for Diseases Control and the World Health Organization has and continues to do research on developing, studying long term immunity, and herd immunity.

First, it is necessary to understand the structure and normal characteristics of the variola virus. The Variola virus is a double-stranded DNA virus, it contains two envelopes; the outer envelope is present only in the extracellular state. The core of the virus contains lipids and proteins and has complex symmetry. The core of the structure contains double stranded DNA and to date, ten enzymes are known to mediate its gene expression and tons of nucleoproteins. The most widely used virus for smallpox inoculation has been vaccinia, which belongs to the genus Orthopoxvirus along with variola virus. Other species of Orthopoxvirus include cowpox (the virus used by Jenner and mentioned above), monkeypox, and camelpox, among others. Its origin is uncertain, and there are many strains of vaccinia with different biological properties. Vaccinia induces both cellular and
humoral immunity to variola virus.
To date, there are six vaccines used to vaccinate the public. Each vaccine elicits its own response. The development of Dyvax was created using a similar virus to that of the small pox. It was created from the cowpox virus. The vaccine is administered with a lancet on the arm. After a few days there will be a pustule which suggest that there was an immunity reaction. The Dryvax vaccine red flags the humoral and the adoptive immunity by producing effector B cells and plasma cells. In an experiment conducted by Dr.Shane Crotty of the La Jolla Institute for Allergy and Immunology and colleagues, Crotty cleverley performed
cutting edge research on the life expectancy of plasma cells. Long-lived plasma cells and memory B cells are responsible for the long-term humoral elicited by most of the vaccines (Crotty 2003). As predicted, plasma cells, upun first vaccination is responsible for the continuous maintenance of the vaccine; this is after antibody reaction. It is critical to also mention that since the vaccination program has stopped since the declared eradication of the disease in 1972(Centers for Disease Control),that memory after DryVax is a valuable benchmark for understanding the longevity of B cell memory in absence of re-exposure to antigen. Crotty’s main objective was to examine the amount of circulating B cells after vaccination. The basis of Crotty’s experimental design: “Study subjects were all normal healthy volunteers. The date postvaccination used in the data analysis is the date of the most recent smallpox vaccination that an individual reported. Nine of 27 of the individuals vaccinated >1 year ago received multiple vaccinations. Seven of those individuals were vaccinated twice (once as a child and once as an adolescent, teenager, or adult), one individual was vaccinated three times, and one individual was vaccinated four times over a 25-year period. In the instances of multiple smallpox vaccinations, the year of the most recent vaccination was used to establish the years postvaccination of the vaccinee in all data analysis” (Crotty; The Journal of Immunology 2003)
Upon conducting clever design to obtain a plausible count of memory cells, the results were indicative of longevity. However, to better characterized and have clear and ut results, Crotty and his team developed an ELISPOT-based assay to better quantitate antigen specific B cells. The results were as follows: antigen (Ag) specific B cells were detected in the blood of small pox vaccine (using the DryVax). Another group of individuals that were VV-immunized (another type of vaccines) and their blood was sampled 4wk postvaccination and approximately 1.5% of circulating IgG+ memory B cells were VV specific at this time. This indicates that there was a response and perhaps a booster should be given if numbers were compared for different vaccines to examine maximum IgG+ plasma B cell circulation. However, this is only 4k postvaccination, as most boosters are given per 8k. Also, Crotty adds that this approximation of circulating B cells is quite large for a specific virus response. To add to the long term immunity, VV-specific memory B cells were detected in Crotty’s sample, even up to 60 years post vaccination. However, the graph at the end of the paper indicates an exponential decay curve kinetics, with a half life of less than 1 years. Short-term vs long term statistical testing was done and indicated comparative p values (reject p if p is less that critical value fail to reject if greater than or equal to critical), <1year and 20-60 years for long term. There was a “build up’’ of immunity after more than a year, as p was greater than the critical value of 0.5. Thus, these results indicate that VV-specific memory B cells are maintained for greater than 50 years in vaccines. Additional test were performed to check the presence of VV-specific Abs and anti-VV Abs were detected in 35/38 individuals. This data is relevant to long term immunity, however, ELISA testing of individuals who have already had the vaccines decades ago. So, for knowledge and understanding of long-term immunity, our repertoire of immune cells, particularly plasma cells and the humoral immunity, there is a substantial memory scaffold available for if the body is attacked by the antigen; this is up to forty years in the study cases. There are several vaccines available to elicit an immune response to the variola virus. However, the DryVax vaccine has been the “one” of choice or preferred vaccination by care providers when vaccination was required. The development strategy for the DryVax vaccine is very similar to the one Jenner obtained. There are just more chemicals to almost neutralize the virus although the virus is considered live. As mentioned earlier, the cow pox virus was is essentially the vaccine to protect the population from the variola virus. The question now is how are the DryVax vaccine made? The Smallpox Vaccine, Dried, Calf Lymph Type, Dryvax, is a live-virus preparation of vaccinia virus derived from the New York City Board of Health vaccinia strain, prepared from calf lymph. The calf lymph is purified, concentrated, and dried by lyophilization. During processing, polymyxin B sulfate, dihydrostreptomycin sulfate, chlortetracycline hydrochloride, and neomycin (these are antibiotics) sulfate are added, and trace amounts of these antibiotics may be present in the final product. Developmental stratigies are only different in this time of error because the scientific community knows more about the virus and how to, for the most part, know how to prepare the vaccine (antibiotics, certain amount of strains of the virus etc), without causing major vaccine side effects. Speaking of complications from the vaccination, however, there are contraindications when giving this vaccine. Immuno-compromised patients (such as those with HIV or any LUPUS, etc) should not be given the vaccination because there were major complications post vaccination; essentially, the complication was due to the lack of immune-participation. Acute myocarditis was also observed in a small percentage of healthy receiving DryVax individuals. However, a correlation between the DryVax individuals and the myocarditis was not detected, so those with preexisting heart abnormalities should not be vaccinated (it is suggested in only emergency situation such as bioterrorism). So developmental strategies are aimed more towards in the case of bioterrorism. Since the US’s eradication of the disease decades ago. According to the NCBI, the herd immunity effect has had a major impact in the eradication of smallpox and many other diseases. The concept and importance of heard immunity comes into play because some individuals in the population may not be able to receive the vaccine due to the fore-mentioned reasons (immunocompromised), this is when the herd immune concept fall into play. The proportion of individuals vaccinated as opposed to those that were not/ are not vaccinated is greater. This decreases the chances of transmission of the virus, which is obviously preferred. In conclusion of heard immunity, in the case of smallpox, scientists calculated that if the critical herd immunity percentage could be maintained in enough locations for a long enough period of time, smallpox would be eradicated forever. In 1967, a year in which smallpox infected an estimated 15 million people leading to 2 million deaths, the World Health Organization (WHO) launched an intensive campaign to eradicate smallpox through vaccination.
In a massive display of world-wide agreement and vaccine distribution, the global eradication of smallpox was evolved in the year 1977, a huge step for man-kind. Though the last case of smallpox in the United States was recorded in 1949, in order to maintain herd immunity in this country, routine vaccination continued until 1971.
According to some sources, “If more people had chosen not to vaccinate their children, as the disease became less common, our population could have dropped below the critical herd immunity percentage.” Thus, the global eradication initiative would have been in jeopardy, and there would be a good chance our children would still need a smallpox vaccine today. Instead, in 2007, the only remaining sign of smallpox is the small scar on the upper arms of many who received the smallpox vaccine decades ago.
Small pox otherwise known as Variola virus was the first disease to be deemed eradicated from the US population. This was in huge efforts of many scientist mentioned earlier. The immune response, mainly hurmoral with plasma cells and effector cells paly a huge role in the longevity of the disease. Also, the fact that the cow pox virus is the center of protection from the variola virus, gives the population double immunity. Heard immunity also play an important role in unvaccinated individuals as the degree of transmission is lower in vaccinated people. There are many more development strategies that aim towards protecting human physiology.