The nonreplicating smallpox candidate vaccines defective vaccinia Lister (dVV-L) and modified vaccinia Ankara (MVA) elicit robust long-term protection

Current smallpox vaccines are live vaccinia viruses that replicate in the vaccinee inducing immunity against the deadly disease smallpox. Replication resulting in virus spread within the host, however, is the major cause of severe postvaccinal adverse events. Therefore, attenuated strains such as modified vaccinia Ankara (MVA) or LC16m8 are candidates as next generation vaccines. These strains are usually grown in primary cells in which mass production is difficult and have an unknown protective potential in humans. Proven vaccine strains of defined origin and modern production techniques are therefore desirable. In this study, defective vaccinia virus (dVV) lacking a gene essential for replication (derived from the Lister vaccine in a complementing cell line) was compared with the Wyeth smallpox vaccine strain and with MVA in mouse animal models using cowpox and ectromelia virus challenge. Similar to MVA, prime-boost immunizations with defective vaccinia induced robust long-term immunity, suggesting it as a promising next generation smallpox vaccine.     

Enhanced safety surveillance study of ACAM2000 smallpox vaccine among US military service members

ObjectivesTo evaluate the rates of myopericarditis (primary objective) and rates of cardiovascular and neurological adverse events (secondary objectives) in temporal association with ACAM2000® smallpox vaccine.MethodsObservational cohort study conducted through monthly surveillance from 2009 to 2017 of electronic medical records of military service members (SM) for pre-specified cardiac and neurological International Classification of Diseases (ICD) codes reported in the 30 days following smallpox vaccination. ICD codes potentially predictive of myopericarditis and codes for encephalitis, Guillain-Barré syndrome, and sudden death were classified into Group 1. All other cardiovascular and neurological ICD codes were classified into Group 2. Medical records containing Group 1 codes were individually reviewed to confirm coding accuracy and to seek additional data in support of myopericarditis adjudication, which was performed by an independent clinical panel. Chart reviews were not performed for Group 2 codes, which were reported in aggregate only.Results897,227 SM who received ACAM2000 smallpox vaccine and 450,000 SM who received Dryvax smallpox vaccine were included in the surveillance population. The rate of adjudicated myopericarditis among ACAM2000 smallpox vaccine recipients was 20.06/100,000 and was significantly higher for males (21.8/100,000) than females (8.5/100,000) and for those < 40 years of age (21.1/100,000) than for those 40 years or older (6.3/100,000). Overall rates for any cardiovascular event (Group 1 plus Group 2) were 113.5/100,000 for ACAM2000 vaccine and 439.3/100,000 for Dryvax vaccine; rate ratio, 0.26 (95% CI, 0.24–0.28). The rates of subjects with one or more defined neurological events were 2.12/100,000 and 1.11/100,000 for ACAM2000 and Dryvax vaccines respectively; rate ratio, 1.91 (95% CI, 0.71–5.10).ConclusionsElectronic records surveillance of the entire vaccinated SM population over a ten-year period found rates of myopericarditis, of defined neurological events, and of overall cardiac events that were consistent with those of prior passive surveillance studies involving Dryvax or ACAM2000 smallpox vaccines.Clinical trials registration: ClinicalTrials.gov NCT00927719.     

Vaccinia virus strain LC16m8 defective in the B5R gene keeps strong protection comparable to its parental strain Lister in immunodeficient mice

BackgroundAttenuated vaccinia virus strain, LC16m8, defective in the B5R envelope protein gene, is used as a stockpile smallpox vaccine strain in Japan against bioterrorism: the defect in the B5R gene mainly contributes to its highly attenuated properties.MethodsThe protective activity of LC16m8 vaccine against challenge with a lethal dose of vaccinia Western Reserve strain was assessed in wild-type and immunodeficient mice lacking CD4, MHC class I, MHC class II or MHC class I and II antigens.ResultsThe immunization with LC16m8 induced strong protective activity comparable to that of its parent strain, Lister (Elstree) strain, in wild-type mice from 2 days to 1 year after vaccination, as well as in immunodeficient mice at 2 or 3 weeks after vaccination. These results implicated that the defect in the B5R gene hardly affected the potential activity of LC16m8 to induce innate, cell-mediated and humoral immunity, and that LC16m8 could be effective in immunodeficient patients.ConclusionLC16m8 with truncated B5 protein has an activity to induce immunity, such as innate immunity and subsequent cell-mediated and humoral immunity almost completely comparable to the activity of its parental strain Lister.     

Smallpox vaccine,ACAM2000: Sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response

The U.S. Department of Defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (VACV)-based smallpox vaccine. Autoinoculations and secondary and tertiary transmissions due to VACV shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. The objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the application of povidone iodine ointment (PIO) to the vaccination site inactivates VACV without affecting the immune response. These objectives were tested in 60 individuals scheduled to receive smallpox vaccine. Thirty individuals (control) did not receive PIO; 30 subjects (treatment) received PIO starting on post-vaccination day 7. Counter to current dogma, this study showed that VACV continues to shed from the vaccination site after the scab separates. Overall viral shedding levels in the PIO group were significantly lower than those in the control group (p = 0.0045), and PIO significantly reduced the duration of viral shedding (median duration 14.5 days and 21 days in the PIO and control groups, respectively; p = 0.0444). At least 10% of control subjects continued to shed VACV at day 28, and 3.4% continued to shed the virus at day 42. PIO reduced the proportion of subjects shedding virus from the vaccination site from day 8 until days 21–23 compared with control subjects. Groups did not differ significantly in the proportion of subjects mounting an immune response, as measured by neutralizing antibodies, IgM, IgG, and interferon-gamma enzyme-linked immunospot assay. When applied to the vaccination site starting on day 7, PIO reduced viral shedding without altering the immune response. The use of PIO in addition to a semipermeable dressing may reduce the rates of autoinoculation and contact transmission originating from the vaccination site in smallpox-vaccinated individuals.     

接种天花疫苗对猴痘病毒感染的保护作用研究进展

2022年,猴痘疫情从区域的地方性流行扩大至全球暴发,并被WHO列为国际关注的突发公共卫生事件。由于正痘病毒之间的基因序列具有高度相似性且正痘病毒可诱发交叉反应型抗体,接种天花疫苗可能会影响猴痘病毒感染诱导的免疫应答水平及感染者的健康结局。分析天花疫苗接种对猴痘病毒感染的保护作用将有助于确定疫情防控策略和措施。因此,本文通过了解既往猴痘疫情中天花疫苗的接种情况及其健康结局,综述天花疫苗接种、免疫应答情况和临床数据之间的关联性,为猴痘疫情的预防控制策略提供科学证据。     

Adventitious agents and smallpox vaccine in strategic national stockpile

In keeping with current standards, we urge that old smallpox vaccines that were made in animal skin and are still a key part of our strategic national stockpile be tested for adventitious infectious agents. The advisory especially applies to viruses that have the potential for zoonotic transmission to human vaccine recipients.     

Bioterrorism: is it a real threat?

The Geneva Protocol of 1925 commits the signatory nations to refraining from the use of biological weapons. However, the terrorist assaults of September 2001 and, subsequently, the anthrax-containing letters are cause for great concerns: new threats to the security of nations are expected, as terrorist organizations seem to increasingly explore novel ways of spreading terror.In this context, naturally emerging diseases such as SARS, monkeypox or West Nile fever assume new importance because it is difficult to distinguish between natural epidemics and possible bioweapon assaults. Great efforts on the part of governments and public health authorities are necessary to counteract these threats.