Smallpox in Europe, 1950-1971

Mack, Thomas M.

doi:10.1093/infdis/125.2.161

Cited by 158 publications

(106 citation statements)

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“…This is consistent with the known efficacy of postexposure vaccination in the worldwide smallpox eradication campaign (8). In addition, the longevity of immune memory to smallpox seen in this study is consistent with epidemiologic work suggesting that immunity to smallpox disease and death is still present decades after vaccination (8,22,23).…”

Section: Discussionsupporting

confidence: 90%

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

Crotty

Felgner

Davies

et al. 2003

The Journal of Immunology

607

508

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Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (DryVax) is a valuable benchmark for understanding the longevity of B cell memory in the absence of re-exposure to Ag. In this study, we demonstrate that smallpox vaccine-specific memory B cells last for >50 years in immunized individuals. Virus-specific memory B cells initially declined postimmunization, but then reached a plateau ∼10-fold lower than peak and were stably maintained for >50 years after vaccination at a frequency of ∼0.1% of total circulating IgG+ B cells. These persisting memory B cells were functional and able to mount a robust anamnestic Ab response upon revaccination. Additionally, virus-specific CD4+ T cells were detected decades after vaccination. These data show that immunological memory to DryVax vaccine is long-lived and may contribute to protection against smallpox.

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Section: Discussionsupporting

confidence: 90%

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

Crotty

Felgner

Davies

et al. 2003

The Journal of Immunology

607

508

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“…Historical studies indicate that immunity against smallpox wanes over time with the severity of disease increasing steadily as a function of time since vaccination (18). However, immunity against lethal smallpox infection does not change appreciably over time (18,24,33) with survival rates of 98, 94, and 93% during intervals of 0 to 10 years, 11 to 20 years, or Ͼ20 years postvaccination, respectively (24,33). These historical findings, in combination with the results of the T-cell analysis described here, suggests that T-cell memory may play a role in reducing disease severity after exposure to smallpox but that T cells are unlikely to be the sole component of protective immunity since antiviral T-cell responses decline markedly over time ( Fig.…”

Section: Discussionmentioning

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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“…Inoculation by skin scratch appears to be the predominant means for zoonotic infections with CPXV. Because vaccination for orthopoxviruses is no longer routinely recommended for the general public, in part due to significant side effects, vaccine-unprotected individuals will grow in number, and even among vaccinated subjects, immunity may wane (9,10). Moreover, immunocompromised patients and those with atopic dermatitis are particularly susceptible to severe infections (11).…”

mentioning

confidence: 99%

Interferon-γ mediates chemokine-dependent recruitment of natural killer cells during viral infection

Pak-Wittel¹,

Yang²,

Sojka³

et al. 2012

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

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Natural killer (NK) cells provide in vivo control of orthopoxvirus infections in association with their expansion in the draining lymph node (LN), where they are normally very rare. The mechanism of this expansion is unclear. Herein, we determined that NK-cell depletion results in enhanced infection following footpad inoculation of cowpox virus, a natural pathogen of rodents. Following cowpox virus infection in normal mice, NK cells were greatly expanded in the draining LN, were not replicating, and displayed markers similar to splenic NK cells, suggesting specific recruitment of splenic NK cells rather than in situ proliferation. Moreover, NK-cell expansion was abrogated by prior injection of clodronate-loaded liposomes, indicating a role for subcapsular sinus macrophages. Furthermore, recruitment of transferred splenic NK cells to the draining LN was pertussis toxin-sensitive, suggesting involvement of chemokine receptors. Comprehensive analysis of chemokine mRNA expression in the draining LN following infection suggested the selective involvement of CCR2, CCR5, and/or CXCR3. Mice deficient for CCR2 or CCR5 had normal NK-cell recruitment, whereas CXCR3-deficient mice displayed a major defect, which was NK cell-intrinsic. Interestingly, both induction of transcripts for CXCR3 ligands (Cxcl9 and Cxcl10) and NK-cell recruitment required IFN-γ. These data indicate that NK-cell recruitment is mediated by subcapsular sinus macrophages, IFN-γ, and CXCR3 during orthopoxvirus infection.

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Smallpox in Europe, 1950-1971

Cited by 158 publications

References 0 publications

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

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

Interferon-γ mediates chemokine-dependent recruitment of natural killer cells during viral infection

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