Impact of infection or vaccination on pre-existing serological memory
ABSTRACT Once established, serum antibody responses against a specific pathogen may last a lifetime. We describe a cohort of four subjects who received smallpox vaccination, and a single subject who received multiple vaccinations, with antibody levels to unrelated antigens monitored for 1-3years. These immunizations provided the opportunity to determine if infection/vaccination and the resulting toll-like receptor stimulation would alter antigen-specific serological memory to other antigens, including bacterial toxins (tetanus, diphtheria, and pertussis) and viruses (yellow fever virus, measles, mumps, rubella, Epstein-Barr virus, and varicella-zoster virus). Our results indicate that serum IgG levels are remarkably stable and infection or vaccination are unlikely to increase or decrease pre-existing antigen-specific antibody responses.
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ABSTRACT: Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.PLoS ONE 11/2013; 8(11):e81752. DOI:10.1371/journal.pone.0081752 · 3.53 Impact Factor
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ABSTRACT: Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions, we may be able to elicit more effective and long-lived immunity with fewer vaccinations.Vaccine 04/2014; 32(25). DOI:10.1016/j.vaccine.2014.03.078 · 3.49 Impact Factor
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ABSTRACT: The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM+ and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM+, switched (IgA+/IgG+), IgM+ only, IgD+ only, and CD27- (IgA+/IgG+/IgM+)] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.PLoS ONE 05/2014; 9(5):e97087. DOI:10.1371/journal.pone.0097087 · 3.53 Impact Factor