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

Crotty, Shane; Felgner, Phil; Davies, Huw C.; Glidewell, John; Villarreal, Luis P.; Ahmed, Rafi

doi:10.4049/jimmunol.171.10.4969

Cited by 607 publications

(563 citation statements)

References 22 publications

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“…Antibody production can be extremely long-lived and is thought to be a major mechanism of long-term protection from pathogens [8,9]. As individuals age their ability to generate high-affinity antibodies that can protect from infection wanes.…”

Section: Effect Of Age On Cd4 + T-cell-and Humoral-mediated Memorymentioning

confidence: 99%

The effect of aging on cognate function and development of immune memory

Haynes

2005

Current Opinion in Immunology

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Immunological memory is one of the central features of the immune system and can be described as the ability of the immune system to respond more efficiently to a second encounter with the same pathogen. The immune system is dramatically affected by age-related changes and it is becoming apparent that immune memory exhibits significant defects as a result of aging. Although immune memory generated during youth functions well into old age, that generated later in life functions poorly. Importantly, age-related defects in the cognate helper function of CD4 + T cells can potentially influence the development of both humoral and cell-mediated immune memory. These defects ultimately result in aged individuals who exhibit reduced responses to both infections and vaccinations.

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Section: Effect Of Age On Cd4 + T-cell-and Humoral-mediated Memorymentioning

confidence: 99%

The effect of aging on cognate function and development of immune memory

Haynes

2005

Current Opinion in Immunology

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“…Memory B cells are thought to be responsible for the secondary (anamnestic) immune response to an Ag (18)(19)(20) and, indirectly, Ab persistence (18), by replenishing the pool of long-lived Agspecific plasma cells [which are responsible for the continuous maintenance of serum Ab levels (21)(22)(23)]. It is thought that at steady state (.1 y following vaccine Ag encounter), memory B cells, plasma cells, and Abs are part of a robust homeostatic system (24).…”

mentioning

confidence: 99%

B Cell Memory to a Serogroup C Meningococcal Conjugate Vaccine in Childhood and Response to Booster: Little Association with Serum IgG Antibody

Perrett

Jin

Clutterbuck

et al. 2012

The Journal of Immunology

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The maintenance of adequate serum Ab levels following immunization has been identified as the most important mechanism for individual long-term protection against rapidly invading encapsulated bacteria. The mechanisms for maintaining adequate serum Ab levels and the relationship between Ag-specific memory B cells and Ab at steady state are poorly understood. We measured the frequency of circulating serogroup C meningococcal (MenC)-specific memory B cells in 250 healthy 6- to 12-y-old children 6 y following MenC conjugate vaccine priming, before a booster of a combined Haemophilus influenzae type b–MenC conjugate vaccine and then 1 wk, 1 mo, and 1 y after the booster. We investigated the relationship between circulating MenC-specific memory B cell frequencies and Ab at baseline and following the booster vaccine. We found very low frequencies of circulating MenC-specific memory B cells at steady state in primary school-aged children and little association with MenC IgG Ab levels. Following vaccination, there were robust memory B cell booster responses that, unlike Ab levels, were not dependent on age at priming with MenC. Measurement of B cell memory in peripheral blood does not predict steady state Ab levels nor the capacity to respond to a booster dose of MenC Ag.

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“…Poxvirus-specific Ab titers are stable for the entire human lifespan and T cell immunity is maintained for decades (7,8). Therefore, orthopoxviruses mainly infect unvaccinated individuals.…”

mentioning

confidence: 99%

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Dasgupta

Hammarlund

Slifka

et al. 2007

The Journal of Immunology

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Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Different from other poxviral subfamilies, however, orthopoxviruses are not known to evade recognition by CTL. In fact, vaccinia virus (VV) is used as a vaccine against smallpox and a vector for eliciting strong T cell responses to foreign Ags. and both human and mouse T cells are readily stimulated by VV-infected APC in vitro. Surprisingly, however, CD8+ T cells of mice infected with cowpox virus (CPV) or VV recognized APC infected with VV but not APC infected with CPV. Likewise, CD8+ T cells from vaccinated human subjects could not be activated by CPV-infected targets and CPV prevented the recognition of VV-infected APC upon coinfection. Because CD8+ T cells recognize viral peptides presented by MHC class I (MHC I), we examined surface expression, total levels, and intracellular maturation of MHC I in CPV- and VV-infected human and mouse cells. Although total levels of MHC I were unchanged, CPV reduced surface levels and inhibited the intracellular transport of MHC I early during infection. CPV did not prevent peptide loading of MHC I but completely inhibited MHC I exit from the endoplasmic reticulum. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-infected cells “invisible” to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.

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

Cited by 607 publications

References 22 publications

The effect of aging on cognate function and development of immune memory

The effect of aging on cognate function and development of immune memory

B Cell Memory to a Serogroup C Meningococcal Conjugate Vaccine in Childhood and Response to Booster: Little Association with Serum IgG Antibody

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

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