Frequency of Adverse Events after Vaccination with Different Vaccinia Strains

Abstract

BackgroundLarge quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus.Methods and FindingsWe analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect that showed decreasing incidences of adverse events over several decades. To estimate death rates, we then restricted our analysis to more-recent studies. We estimated that vaccination with the NYCBH strain leads to an average of 1.4 deaths per million vaccinations (95% credible interval, 0–6) and that vaccination with Lister vaccine leads to an average of 8.4 deaths per million vaccinations (95% credible interval, 0–31). We combined age-dependent estimates of the frequency of death after vaccination and revaccination with demographic data to obtain estimates of the expected number of deaths in present societies due to vaccination with the NYCBH and Lister vaccinia strains.ConclusionsPrevious analyses of smallpox vaccination policies, which rely on the commonly assumed value of one death per million vaccinations, may give serious underestimates of the number of deaths resulting from vaccination. Moreover, because there are large, strain-dependent differences in the frequency of adverse events due to smallpox vaccination, it is difficult to extrapolate from predictions for the ...

Targeted delivery of a suicide gene to human colorectal tumors by a conditionally replicating vaccinia virus

“…43 Furthermore, the vaccine Copenhagen strain was approved for human vaccine use in Denmark and the Netherlands. 44 A recombinant of the Copenhagen strain expressing the rabies virus glycoprotein was constructed by the insertion of the encoding cDNA in the TK locus. 45 This recombinant has received a conditional commercial license in both Europe and in the United States.…”

Proteome‐wide analysis of the serological response to vaccinia and smallpox

“…This was achieved without a real understanding of the immunology underlying the protection. The risk of adverse reactions associated with live vaccinia [1,2] led to the eventual withdrawal of the licensed Dryvax ® vaccine from general use in 1972, although the potential re-emergence of smallpox as a weapon of bioterrorism has sparked renewed interest in vaccinia and the development of safer alternatives, such as the attenuated modified virus Ankara (MVA) strain. The immunological basis of protection against smallpox afforded by vaccinia is now being re-examined using modern genetic, immunological and proteomic techniques.…”

Targeting the vaccinia virus L1 protein to the cell surface enhances production of neutralizing antibodies

“…Because of these health risks, vaccination is contraindicated in pregnant women, the immunocompromised, and in persons with dermatological abnormalities, such as eczema [7][8][9]. Kretzschmar et al recently reported that the frequency of death associated with vaccination might be higher than previously believed [10]. To diminish these health risks, attenuated VACV viruses, such as modified vaccinia Ankara (MVA) and LC8m16 have been developed [11][12][13][14].…”