The elderly population is more susceptible to infections as a result of an altered immune response, commonly referred to as immunosenescence. Cytomegalovirus (CMV)-infection associated changes in blood lymphocytes are known to impact this process, but the interaction with gender remains unclear. Therefore, we analysed the effects and interaction of gender and CMV on the absolute numbers of a comprehensive set of naive and memory T- and B-cell subsets in people between 50 and 65 years of age. Enumeration and characterisation of lymphocyte subsets by flow cytometry was performed on fresh whole blood samples from 255 middle-aged persons. CMV-IgG serostatus was determined by ELISA. Gender was a major factor affecting immune cell numbers. CMV infection was mainly associated with an expansion of late-differentiated T-cell subsets. CMV+ males carried lower numbers of total CD4+, CD4+ central memory (CM) and follicular helper T-cells than females and CMV− males. Moreover, CMV+ males had significantly lower numbers of regulatory T (Treg)-cells and memory B-cells than CMV+ females. We here demonstrate an interaction between the effects of CMV infection and gender on T- and B-cells in middle-aged individuals. These differential effects on adaptive immunity between males and females may have implications for vaccination strategies at middle-age.
Rapid antibody responses after challenge with oral polio vaccine provide evidence for poliovirus-specific memory immunity in seronegative elderly people. However, in contrast to preexisting immunity, memory immunity does not protect against virus excretion. These results have important implications for the poliomyelitis-eradication initiative, in particular for future immunization policies after eradication has been achieved.
Objectives Cytomegalovirus infection is thought to affect the immune system and to impact general health during ageing. Higher CMV‐specific antibody levels in the elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally differentiated and CMV‐specific T cells are hallmarks of CMV infection, which are thought to expand over time, a process also referred to as memory inflation. Methods We studied CMV‐specific antibody levels over ~ 27 years in 268 individuals (aged 60–89 years at study endpoint), and to link duration of CMV infection to T‐cell numbers, CMV‐specific T‐cell functions, frailty and cardiovascular disease at study endpoint. Results In our study, 136/268 individuals were long‐term CMV seropositive and 19 seroconverted during follow‐up (seroconversion rate: 0.56%/year). CMV‐specific antibody levels increased slightly over time. However, we did not find an association between duration of CMV infection and CMV‐specific antibody levels at study endpoint. No clear association between duration of CMV infection and the size and function of the memory T‐cell pool was observed. Elevated CMV‐specific antibody levels were associated with the prevalence of cardiovascular disease but not with frailty. Age at CMV seroconversion was positively associated with CMV‐specific antibody levels, memory CD4 + T‐cell numbers and frailty. Conclusion Cytomegalovirus‐specific memory T cells develop shortly after CMV seroconversion but do not seem to further increase over time. Age‐related effects other than duration of CMV infection seem to contribute to CMV‐induced changes in the immune system. Although CMV‐specific immunity is not evidently linked to frailty, it tends to associate with higher prevalence of cardiovascular disease.
The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response.
The emergence of the A(H1N1) 2009 pandemic influenza virus was initially seen as a major world-wide health concern since a low degree of immunity to this virus strain was anticipated. However, age-specific infection attack rates and age-specific differences in seroresponse indicate that pre-existing immunity may have played a significant role in protection especially in older age groups. This study describes the use of a protein microarray as a multiplex analysis tool for detection of influenza virus H1 strain-specific memory B-cells before and after infection with A(H1N1)pdm09. The discrimination was based on detection of specific antibodies in culture supernatants from polyclonally stimulated B-cells against recombinant influenza virus HA1 proteins representing influenza virus subtypes H1 through H9. The protein microarray proved sensitive and specific for antibody detection in culture supernatants of B-cells, and with the potential to deduce a person's history of infection with particular influenza virus variants, including A(H1N1)pdm09. Blood samples obtained from different age groups prior to the pandemic in 2009 partly showed the presence of B-cells producing antibodies binding to the closely related A(H1N1) 1918 pandemic influenza virus, and of which the magnitude increased with age. These cross-reactive antibodies were produced by single memory B-cells present in these donors, and either bind to epitopes on HA1 which are shared within different H1 strains (homosubtypic response) or shared between different subtypes (heterosubtypic response).
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