Eradication Of Smallpox Research Articles

Recombinant chimeric horsepox virus (TNX-801) is attenuated relative to vaccinia virus strains in both in vitro and in vivo models.

Variola and monkeypox viruses are medically important pathogens that can cause fatal human disease. The two FDA-approved vaccines, ACAM-2000 and JYNNEOS, have important advantages and disadvantages. ACAM-2000 offers durable immunity; however, it has high adverse event rates. In contrast, JYNNEOS has a safer profile but requires two doses 4-weeks apart to achieve comparable immunity. Consequently, there is a need for vaccines offering durable immunity via single immunization with minimal adverse events. TNX-801 is a preclinical stage vaccine that can stimulate potent immunity via a single dose and provides protection against lethal mpox disease in the nonhuman primate model. Here, we show that TNX-801 is >10- to 1,000-fold attenuated in in vitro and in vivo models including human primary cells and immunocompromised murine models than vaccine strains utilized in smallpox eradication. The natural attenuation of TNX-801 and its ability to induce protective immunity via a single vaccination are promising and warrants further development.

Enhanced Expression of the L1R Gene of Vaccinia Virus by the tPA Signal Sequence Inserted in a Fowlpox-Based Recombinant Vaccine.

The use of Vaccinia virus (VACV) as a preventive vaccine against variola, the etiological agent of smallpox, led to the eradication of smallpox as a human disease. The L1 protein, a myristylated transmembrane protein present on the surface of mature virions, plays a significant role in infection and morphogenesis, is well-conserved in all orthopoxviruses, and is the target of neutralizing antibodies. DNA recombinant vaccines expressing this protein were successfully used, but they showed lower efficacy in non-human and human primates when used alone, and viral-vectored fowlpox vaccines were already proved to increase immunogenicity when used as a boost. Here, we constructed a novel fowlpox-based recombinant (FPtPA-L1R), in which the tissue plasminogen activator signal sequence was linked to the 5' end of the L1R gene to drive the L1 protein into the cellular secretion pathway. FPtPA-L1R expresses a functional heterologous protein that can be immunoprecipitated by hyperimmune rabbit serum. The protein shows cytoplasmic and membrane subcellular localizations and long-lasting expression in CEF, non-human primate Vero and human MRC-5 cells. The tissue plasminogen activator signal sequence can thus contribute significantly to the expression of the L1 protein and may enhance the immunogenicity of a putative DNA/FP prime-boost vaccine.

Edward Jenner: A Beacon of Hope in the Age of Disease.

Edward Jenner, born in 1749 in Berkeley, Gloucestershire, England is widely recognized as the pioneer of the smallpox vaccine, a breakthrough that paved the way for the eventual eradication of the disease. This article traces Jenner's journey from his early education and apprenticeship under renowned surgeon John Hunter to his groundbreaking work on vaccination. Jenner's keen observations led him to hypothesize that cowpox could provide immunity against smallpox, which he confirmed through an experiment in 1796. Despite initial skepticism and the continued practice of variolation, Jenner's findings gained acceptance, and his work laid the foundation for modern immunology. The article also explores Jenner's personal life, his contributions to the medical community, and the eventual global impact of his work, culminating in the eradication of smallpox. Jenner's legacy is a testament to the power of scientific inquiry and its transformative effect on public health.

Monkeypox- need for Vigilant Health system and Regulations towards a Global Health Threat

A viral illness caused by the monkey pox virus, monkeypox is now known as Mpox. It is a zoonotic infectious disease causing painful rash, enlarged lymph nodes, fever, headache, muscle ache, backpain and low energy. According to WHO, most cases in 2022 were in Africa but later m-pox was reported from USA, Europe Australia & Canada. Mpox continues to be a threat today, with upsurge of cases in Democratic Republic of Congo and other countries in Africa. Since 2022, there has also been an upsurge in mpox cases and deaths in the Democratic Republic of the Congo. Over 120 countries have reported mpox between Jan 2022-Aug 2024, with over 1,00,000 laboratory-confirmed cases reported and over 220 deaths among confirmed cases. In India, MoHFW reported 30 cases in the last 2022 outbreak, with last case occurring in March 2024. The monkeypox virus was discovered in Denmark (1958) in monkeys kept for research. The first reported human case of mpox was a nine-month-old boy in the Democratic Republic of the Congo (1970). Mpox steadily emerged in central, east and west Africa following the eradication of smallpox in 1980 and the end of smallpox vaccination worldwide. In 2003, there was an outbreak in the United States of America, linked to imported wild animals. Since 2005, thousands of cases are reported in the Democratic Republic of the Congo every year. In May 2022, an outbreak of mpox appeared suddenly and rapidly spread across Europe, the Americas and then all six WHO regions including refugee camps in the Republic of the Sudan.

Norman Vetter: epidemiologist whose work on smallpox eradication in Bangladesh cemented his beliefs on importance of systemic change to improve health

Norman Vetter: epidemiologist whose work on smallpox eradication in Bangladesh cemented his beliefs on importance of systemic change to improve health

Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022.

BackgroundIn 2022, a global monkeypox virus (MPXV) clade II epidemic occurred mainly among men who have sex with men. Until early 1980s, European smallpox vaccination programmes were part of worldwide smallpox eradication efforts. Having received smallpox vaccine > 20 years ago may provide some cross-protection against MPXV.AimTo assess the effectiveness of historical smallpox vaccination against laboratory-confirmed mpox in 2022 in Europe.MethodsEuropean countries with sufficient data on case vaccination status and historical smallpox vaccination coverage were included. We selected mpox cases born in these countries during the height of the national smallpox vaccination campaigns (latest 1971), male, with date of onset before 1 August 2022. We estimated vaccine effectiveness (VE) and corresponding 95% CI for each country using logistic regression as per the Farrington screening method. We calculated a pooled estimate using a random effects model.ResultsIn Denmark, France, the Netherlands and Spain, historical smallpox vaccination coverage was high (80-90%) until the end of the 1960s. VE estimates varied widely (40-80%, I2 = 82%), possibly reflecting different booster strategies. The pooled VE estimate was 70% (95% CI: 23-89%).ConclusionOur findings suggest residual cross-protection by historical smallpox vaccination against mpox caused by MPXV clade II in men with high uncertainty and heterogeneity. Individuals at high-risk of exposure should be offered mpox vaccination, following national recommendations, regardless of prior smallpox vaccine history, until further evidence becomes available. There is an urgent need to conduct similar studies in sub-Saharan countries currently affected by the MPXV clade I outbreak.

Factors responsible for the re-emergence of Monkeypox and implications for global health

The eradication of smallpox in 1980 and the subsequent discontinuation of smallpox vaccination have resulted in a decline in immunity against orthopoxviruses. As a result, Monkeypox (Mpox) has reappeared as a significant virus with implications for public health. This article aims to determine some of the factors responsible for the re-emergence of Mpox and its implications for global health. A thorough literature search for this present article was conducted through a search of databases and journals, including the WHO and CDC websites, using keywords such as “Monkeypox”, “Re-emergence”, “Prevalence”, “Risk factors”, “Implications” and “Global Health” to find articles published from 2003 to 2023. We found that Mpox recently occurred in several countries in America, Europe, and Asia, including the United States of America (USA), Brazil, Spain, Colombia, Mexico, the United Kingdom (UK), Germany, and Pakistan, between 2022 and 2023. The rise in Mpox cases was also seen, with incidences documented in Western Europe (2599 cases, accounting for 42.76% of the total), Southern Europe (1932 cases, representing 31.79% of the total), Northern Europe (1487 cases, comprising 24.46% of the total), and Eastern Europe (59 cases, making up 0.97% of the total). Possible factors implicated in the re-emergence of MPOX include; the expansion of the human population, increased same sexual intercourse, and poor epidemiological surveillance. etc. The re-emergence of Mpox in the world is a difficult issue that requires world leaders to take a diverse approach to control the disease. World leaders and scientists must pursue natural compounds with antiviral properties. Hopefully, natural products will give alternate therapy alternatives for preventing infection transmission between humans and limiting virus proliferation in host organisms.

Old stories, new cases. Viral infectious diseases and children's health

During the 20th century, smallpox has produced between 300–and 500 million victims. In 1796, Edward Jenner conducted one of the first modern immunizations when he inoculated an 8-year-old boy using material from a cowpox lesion. In 1959, WHO (World Health Organization) launched the Smallpox Eradication Programme. By 1980, WHO declared smallpox officially eradicated. Due to genetic and antigenic similarities between the monkeypox and smallpox viruses, the cessation of smallpox vaccination since 1980′s contributed to the wanning of cross‐protection against monkeypox (mpox). Outbreaks of human mpox has spread across 110 countries.In 1916 and 1952, two major poliovirus outbreaks took place in the USA. The virus killed or paralyzed over half a million people yearly. Introduction of the inactivated polio vaccine (IPV,1955) and oral polio virus (OPV,1963) led to decline in the number of cases by 99.99 %. The Global Polio Eradication Initiative (GPEI) was launched in 1988 and five of six WHO regions have been certified free of wild polio virus (WPV), except Eastern Mediterranean region. Africa had been declared WPV free, unfortunately cases of paralysis due to wild virus in Malawi and Mozambique were detected having been imported from Pakistan. Outbreaks of circulating Vaccine Derived Polio Virus type 2 (cVDPV2) have expanded in the Eastern Mediterranean and African Region from October 2022 to February 2023. Measles, being one of the most contagious infections, requires high population immunity (>95 %) to impede transmission. In 1963, a measles vaccine became available. Finland was the first country to eradicate measles by using the 2 dose-measles vaccines. The region of the Americas was verified to have eliminated measles in 2000. The COVID-19 pandemic disrupted global vaccination activities. Vaccination coverage has fallen from 90 % to 50 % in western countries. Over 30 000 measles cases were reported from 40 WHO European Region members in 2023.

The fight against smallpox during the Savoy kingdom in Genoa between 1815 and 1859.

The article aims to outline the features of the efforts for smallpox eradication within the pre-unitary context of the Kingdom of Sardinia, characterized by a long tradition in medical-health prevention. This tradition is partly inherited from the health magistracies of the Italian states during the ancient regime and partly adopted from policies initially outlined by Napoleon and later by other European states. In addition to prevention activities, authorities also engage in a vigorous information and awareness campaign aimed at eliminating common prejudices and doubts about vaccination among the population. In analyzing the authorities' achievements in combating smallpox, this study examines the two epidemic waves (1829-30 and 1852-54), along with the legislative developments before, during, and after these periods. It also compares these regulatory changes with those in other European contexts. The epidemiological situation turned out to be more complex to manage than the authorities had anticipated, as evidenced by the increasing controls imposed. Scientific and political communities, both in the Kingdom of Sardinia and in other European nations, found themselves divided on the legitimacy of proposing restrictive measures by the state. Some advocated for restricted access to public places and imposed mandatory vaccination for vulnerable individuals. The comparison with smallpox resulted in a gradual improvement in of health security levels, although vaccination coverage did not reach the desired targets. Several factors contributed to this failure, including the limited expertise and reluctance of medical personnel, who were burdened with much of the operation's costs. Additionally, particularly in rural areas, there was widespread mistrust among the population towards doctors. Despite these challenges, the fight against smallpox enabled authorities to develop population control tools in the name of public health protection. However, it was not until 1888 that mandatory vaccination was introduced.

Epidemiological Aspects and Basic Directions of the Protective Medications against Monkeypox Development

Relevance. After smallpox eradication, in conditions of population immunity to orthopoxviruses absence, Monkeypox virus became most significant orthopoxvirus, pathogenic for humans. Therefore the generalization of data on the areas of infection outbreaks, human diseases and methods of prevention and treatment of monkey pox is important task. Aim. To characterize the problem of monkeypox in the world based on an analysis of foreign scientific publications over the past 20 years. Materials and methods. The work used publications presented in the main international medical information databases PubMed, Web of Science, Embase, etc. To analyze the publications, the analytical epidemiological method was used. Results and discussion. Monkeypox virus, obtained and identified in 1958, by genetic and phenotypic differences divides on two clades: West-African with lethality 3.6% and Central-African (Congo Basin) with lethality 10%. Monkeypox virus transmission to men happens in two ways, either from animal-to-human or human-to-human. Monkey pox is endemic only on African continent, but In 2003 year the first outbreak, numbering 47 confirmed cases, was occurred in non-endemic country – USA and the largest monkeypox outbreak began in Nigeria in September 2017 year and continue to the present. Comparison of the genome sequences of strains, isolated from patients in non-endemic countries, showed, that it genetically close to West-african strains, belong to II clades and were descended from a common ancestor. Many cases of disease in humans in the current outbreak have been traced to sexual transmission especially among men, who identify ourselves as gay or bisexual. The basis method for identification of agent in present time is PCR-RT targeting on the tumor necrosis factor (TNF) receptor gene. Usually monkeypox of human is mild, self-limiting disease. The symptoms of monkeypox are varied and non-specific. One of the most frequently observed clinical symptoms is lymphadenopathy. Most patients recover during some weeks. However, specific antiviral treatment – tecovirimat (S-246) and brincidofovir (CMX-001) – may be used for seriously ill or immunocompromised individuals. For prophylactic disease in present time are use vaccines JYNNEOSTM, ACAM2000R and Aventis Pasteur (APSV). Conclusion. General vaccination against monkeypox don't develop accordingly to modern recommendations WHO. Ring vaccination is recommended to conduct for suppression of spread virus in nidus of infection among population. Timely international coordination is needed to prevent the global spread of a disease with epidemic potential.

Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.

Age-related antibody response to Orthopoxviruses and implications for public health measures: Insights from a South Korean study

BackgroundAfter the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV infections after Mpox (formerly monkeypox) occurrences, such as the latest global outbreak in 2022–2023. This study aimed to provide crucial insights for the development of effective public health policy making against mpox in populations residing in regions where the virus is not prevalent. MethodsThis study used enzyme-linked immunosorbent assays (ELISA) to examine smallpox and mpox antibodies in Koreans with three different age groups. We analyzed 56 sera obtained from a tertiary care hospital in South Korea between September 2022 and April 2023. Plasma levels of antibodies against the viral proteins of smallpox (variola cytokine response-modifying protein B) and MPXV (A29) were measured using enzyme-linked immunosorbent assays. ResultsPlasma samples from participants in their early 40 s and older exhibited higher reactivity to viral antigens than those from younger participants. Furthermore, there was a strong positive correlation in antibody positivity for the two different viruses across the sera. ConclusionsThe presence of low antibody levels in participants ˂40 years may hinder their ability to defend against OPXV. Therefore, it is imperative to implement effective public health measures to mitigate the transmission of OPXV within the community. These findings serve as fundamental information for devising strategies to combat mpox efficiently, particularly in regions where the virus is not prevalent.

Navigating resistance in global health governance: Certification of smallpox eradication in China

ABSTRACT Certification is an essential stage in disease eradication efforts, encompassing epidemiological, managerial, and political complexities. The certification of smallpox eradication in the People’s Republic of China (PRC, or China) exemplifies the multifaceted nature of the certification. Despite eradicating smallpox in the early 1960s, before the Global Smallpox Eradication Programme (SEP) intensified in 1967, China was one of the last countries certified as smallpox-free by the World Health Organization (WHO) in 1979. The WHO encountered notable resistance during the certification of smallpox eradication in China. This article examines the underlying motivations propelling China’s resistance, the factors that contributed to the shifts in its stance, the challenges navigated by the WHO, and the ultimate achievement of certification despite controversies surrounding its transparency and credibility. Through the case of the certification of smallpox eradication, the article provides a historical context of China’s selective engagement in global health governance, emphasising the critical importance of building a trusting relationship between the WHO and its member states. It offers insights for fostering effective collaboration among diverse stakeholders driven by varied political agendas in addressing shared global health challenges such as the coronavirus disease (COVID-19) pandemic.

Mpox in humans: an overview of the 2022-2023 epidemic

Monkeypox, also known as Mpox, is a zoonotic disease endemic to central and western Africa. Following the successful eradication of human smallpox, Mpox has emerged as the primary poxvirus-related illness. In May 2022, an outbreak of Mpox was reported in the United Kingdom. Within weeks, cases were identified in multiple countries, leading to a significant increase in its incidence. This outbreak represents the first instance of sustained transmission in non-endemic areas. As of September 2023, there have been 115 affected countries, with over 90,000 confirmed cases and 157 deaths. Notably, over 96% of cases have occurred in individuals assigned male at birth, with a median age of 34 years. While specific antivirals and vaccines for Mpox are currently unavailable, drugs and vaccines originally designed to combat human smallpox have proven to be effective in its management. Nevertheless, the global distribution of these resources remains limited, and many nations continue to face challenges in accessing them. For this review, we consulted statistics published by the WHO and PAHO from May 2022 to September 2023, along with recent articles addressing the clinical characteristics of the infection, treatment options, prevention strategies, and relevant ethical and social issues.

Role of vaccination in patients with human monkeypox virus and its cardiovascular manifestations.

Human monkeypox, caused by the monkeypox virus (MPXV), is an emerging infectious disease with the potential for human-to-human transmission and diverse clinical presentations. While generally considered milder than smallpox, it can lead to severe cardiovascular complications. The virus primarily spreads through contact with infected animals or through human-to-human transmission. Cardiovascular involvement in human monkeypox is rare but has been associated with myocarditis, pericarditis, arrhythmias, and even fulminant myocardial infarction. Vaccination plays a crucial role in preventing and controlling monkeypox, but the eradication of smallpox has left global populations vulnerable. This review explores the cardiovascular manifestations of human monkeypox, the role of vaccination in disease prevention, and the importance of continued research and development of effective vaccines to protect against this emerging infectious threat. The global impact of monkeypox outbreaks, particularly on vulnerable populations, further highlights the importance of understanding and addressing this disease.

An Attenuated and Highly Immunogenic Variant of the Vaccinia Virus.

The vaccinia virus (VACV) has been used for prophylactic immunization against smallpox for many decades. However, the VACV-based vaccine had been highly reactogenic. Therefore, after the eradication of smallpox, the World Health Organization in 1980 recommended that vaccination against this infection be discontinued. As a result, there has been a rise in the occurrence of orthopoxvirus infections in humans in recent years, with the most severe being the 2022 monkeypox epidemic that reached all continents. Thus, it is crucial to address the pressing matter of developing safe and highly immunogenic vaccines for new generations to combat orthopoxvirus infections. In a previous study, we created a LAD strain by modifying the LIVP (L) VACV strain, which is used as a first-generation smallpox vaccine in Russia. This modification involved introducing mutations in the A34R gene to enhance extracellular virion production and deleting the A35R gene to counteract the antibody response to the viral infection. In this study, a strain LADA was created with an additional deletion in the DNA of the LAD strain ati gene. This ati gene directs the production of a major non-virion immunogen. The findings indicate that the LADA VACV variant exhibits lower levels of reactogenicity in BALB/c mice during intranasal infection, as compared to the original L strain. Following intradermal immunization with a 105 PFU dose, both the LAD and LADA strains were found to induce a significantly enhanced cellular immune response in mice when compared to the L strain. At the same time, the highest level of virus-specific IFN-γ producing cells for the LAD variant was detected on the 7th day post-immunization (dpi), whereas for LADA, it was observed on 14 dpi. The LAD and LADA strains induced significantly elevated levels of VACV-specific IgG compared to the original L strain, particularly between 28 and 56 dpi. The vaccinated mice were intranasally infected with the cowpox virus at a dose of 460 LD50 to assess the protective immunity at 62 dpi. The LADA virus conferred complete protection to mice, with the LAD strain providing 70% protection and the parent strain L offering protection to only 60% of the animals.

Emergence of Monkeypox (MPX): A Close Relative of Small Pox During COVID-19 Era.

After the eradication of smallpox (SPX), a new zoonotic threat that can trigger outbreaks has emerged. It may be fatal during the COVID19 outbreak. Humanity continues to be threatened due to re-emergence of the outbreaks. In most cases, new emerging viral agents originate from nonhuman hosts with zoonotic origins. Recent outbreaks of zoonotic infectious diseases with the potential to cause epidemics and pandemics continue to pose a major threat to the health security of entire regions, continents, and the world at large. Around five decades backthat Monkeypox (MPX) was reported for the first time in the Democratic Republic of the Congo (DRC) and was then confined to Central Africa only. Over the time, it has spread to other regions of Africa as well as outside Africa. As of August 2022, 40398 infections have been confirmed in almost 68 countries that have never reported MPX before. The majority of infections have been reported in Europe and Southeast Asia. On 23rd August 2022, MPX was declared a public health emergency of international concern, a step below declaring any disease as a pandemic. The article discusses the recent history of MPX outbreaks, as well as the evolving clinical manifestations of the disease, and the possible causes of the increase in cases, including the cessation of SPX vaccinations.

A field diagnostic method for rapid and sensitive detection of mpox virus.

The mpox outbreak has subdued with fewer reported cases at the present in high-income countries. It is known that mpox virus (MPXV) infection has been epidemic for more than 50 years in African countries. The ancestral MPXV strain has changed into multiple clades, indicating the ongoing evolution of MPXV, which reflects the historical neglect of mpox in Africa, especially after smallpox eradication, and bestows the danger of more severe mpox epidemics in the future. It is thus imperative to continue the development of mpox diagnostics and treatments so we can be prepared in the event of a new mpox epidemic. In this study, we have developed an MPXV detection tool that leverages the recombinase-aid amplification assay by integrating lateral flow strips (RAA-LF) and one-step sample DNA preparation, with visible readout, no need of laboratory instrument, and ready for field deployment. The detection limit reaches 10 copies per reaction. The performance of our RAA-FL assay in diagnosing mpox clinical samples is on par with that of the quantitative polymerase chain reaction (PCR) assay. Taken together, we have developed a point-of-care RAA-LF method of high accuracy and sensitivity, readily deployable for field detection of MPXV. This diagnostic tool is expected to improve and accelerate field- and self-diagnosis, allow timely isolation and treatment, reduce the spread of MPXV, thus effectively mitigate MPXV outbreak in the future.

Comparison of the Efficacy of Different Schemes for Using Recombinant Vector Vaccines against Ebola Fever, Based on Vaccinia Virus, MVA Strain

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

Biology of Variola Virus.

Variola virus is an anthroponotic agent that belongs to the orthopoxvirus family. It is an etiological agent of smallpox, an ancient disease that caused massive mortality of human populations. Twentieth century has witnessed the death of about 300million people due to the unavailability of an effective vaccine. Early detection is the primary strategy to prevent an outbreak of smallpox. Variola virus forms the characteristic pus-filled pustules and centrifugal rash distribution in the infected patients while transmission occurs mainly through respiratory droplets during the early stage of infection. No antiviral drugs are approved for variola virus till date. Generation of first-generation vaccines helped in the eradication of smallpox which was declared by the World Health Organization.