Shining Light on “Dark Winter”

O’Toole, Tara; Mair, Michael; Inglesby, Thomas V.

doi:10.1086/339909

Cited by 140 publications

(67 citation statements)

References 14 publications

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“…Moreover, if the MV vs. TV decision ever has to be made, the value of R 0 will not be known more precisely than at present, and an accurate estimate of the initial attack size may not be available (ref. 16; http:͞͞www.hopkins-biodefense.org͞ lessons.html). Hence, a decision maker concerned with minimizing the number of deaths in the face of this uncertainty should choose TV only if (s)he is quite certain that R 0 and the initial attack size fall in the TV-favorable region of Fig.…”

Section: Sensitivity Analysis and Preattack Vaccinationmentioning

confidence: 99%

Emergency response to a smallpox attack: The case for mass vaccination

Kaplan

Craft

Wein

2002

Proc. Natl. Acad. Sci. U.S.A.

397

308

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In the event of a smallpox bioterrorist attack in a large U.S. city, the interim response policy is to isolate symptomatic cases, trace and vaccinate their contacts, quarantine febrile contacts, but vaccinate more broadly if the outbreak cannot be contained by these measures. We embed this traced vaccination policy in a smallpox disease transmission model to estimate the number of cases and deaths that would result from an attack in a large urban area. Comparing the results to mass vaccination from the moment an attack is recognized, we find that mass vaccination results in both far fewer deaths and much faster epidemic eradication over a wide range of disease and intervention policy parameters, including those believed most likely, and that mass vaccination similarly outperforms the existing policy of starting with traced vaccination and switching to mass vaccination only if required.

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Section: Sensitivity Analysis and Preattack Vaccinationmentioning

confidence: 99%

Emergency response to a smallpox attack: The case for mass vaccination

Kaplan

Craft

Wein

2002

Proc. Natl. Acad. Sci. U.S.A.

397

308

View full text Add to dashboard Cite

show abstract

“…Although several studies have examined the duration of immunity following smallpox vaccination (2,4,9,17,31,35), little is known about the magnitude or duration of immunity following natural smallpox infection itself (32,35). This is an important question because smallpox infection is believed to confer lifelong protective immunity (5), whereas protective immunity following smallpox vaccination represents a topic of considerable debate; protective immunity is either long-lived (2,9,10,15,17,31,33,35) or may persist for only 3 to 5 years (19,21,26,28).…”

mentioning

confidence: 99%

Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study

Hammarlund¹,

Lewis²,

Hanifin³

et al. 2010

J Virol

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Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4؉ and CD8 ؉ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpoxvaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

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“…Given the high mortality rate of smallpox infections in humans and the endemic nature of the disease, smallpox may have caused more human deaths during the past two millennia than any other single disease (27). While wild smallpox no longer exists, variola virus is a potential bioterrorism agent of great concern (3,4,23,44).…”

mentioning

confidence: 99%

Redundancy and Plasticity of Neutralizing Antibody Responses Are Cornerstone Attributes of the Human Immune Response to the Smallpox Vaccine

Benhnia

McCausland

et al. 2008

J Virol

100

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The smallpox vaccine is widely considered the gold standard for human vaccines, yet the key antibody targets in humans remain unclear. We endeavored to identify a stereotypic, dominant, mature virion (MV) neutralizing antibody target in humans which could be used as a diagnostic serological marker of protective humoral immunity induced by the smallpox vaccine (vaccinia virus [VACV]). We have instead found that diversity is a defining characteristic of the human antibody response to the smallpox vaccine. We show that H3 is the most immunodominant VACV neutralizing antibody target, as determined by correlation analysis of immunoglobulin G (IgG) specificities to MV neutralizing antibody titers. It was determined that purified human anti-H3 IgG is sufficient for neutralization of VACV; however, depletion or blockade of anti-H3 antibodies revealed no significant reduction in neutralization activity, showing anti-H3 IgG is not required in vaccinated humans (or mice) for neutralization of MV. Comparable results were obtained for human (and mouse) anti-L1 IgG and even for anti-H3 and anti-L1 IgG in combination. In addition to H3 and L1, human antibody responses to D8, A27, D13, and A14 exhibited statistically significant correlations with virus neutralization. Altogether, these data indicate the smallpox vaccine succeeds in generating strong neutralizing antibody responses not by eliciting a stereotypic response to a single key antigen but instead by driving development of neutralizing antibodies to multiple viral proteins, resulting in a "safety net" of highly redundant neutralizing antibody responses, the specificities of which can vary from individual to individual. We propose that this is a fundamental attribute of the smallpox vaccine.

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Shining Light on “Dark Winter”

Cited by 140 publications

References 14 publications

Emergency response to a smallpox attack: The case for mass vaccination

Emergency response to a smallpox attack: The case for mass vaccination

Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study

Redundancy and Plasticity of Neutralizing Antibody Responses Are Cornerstone Attributes of the Human Immune Response to the Smallpox Vaccine

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