Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Muyanja, Enoch; Ssemaganda, Aloysius; Ngauv, Pearline; Cubas, Rafael; Perrin, Hélène; Srinivasan, Divya; Canderan, Glenda; Lawson, Benton; Kopycinski, Jakub; Graham, Amanda S.; Rowe, Dawne K.; Smith, Michaela J.; Gaucher, Denis; Isern, Sharon; Scott, Michael; Silvestri, Guido; Vanderford, Thomas H.; Castro, Erika; Pantaleo, Giuseppe; Singer, Joel; Gillmour, Jill; Kiwanuka, Noah; Nanvubya, Annet; Schmidt, Claudia; Birungi, Josephine; Cox, Josephine H.; Haddad, Elias K.; Kaleebu, Pontiano; Fast, Patricia E.; Sékaly, Rafick‐Pierre; Trautmann, Lydie

doi:10.1172/jci77956

Cited by 44 publications

(55 citation statements)

References 23 publications

(27 reference statements)

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“…On the contrary, higher antibody titers were associated with higher proportions of putative Tregs, which has previously been linked to delayed T‐cell maturation 4 . In line with our results, young healthy adults in Switzerland had higher yellow fever vaccine (YF17D)‐induced titers compared to vaccinees in Uganda, and the former group presented with lower proportions of memory T‐cell subsets and higher fractions of naive B cells before vaccination 26 . Moreover, viral‐based oral vaccines, for example, bovine rotavirus and polioviruses, are more immunogenic in industrialized than in developing countries, 27 , 28 , 29 but the reasons for these differences are still poorly understood.…”

Section: Discussionsupporting

confidence: 88%

Delayed adaptive immunity is related to higher MMR vaccine‐induced antibody titers in children

et al. 2016

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There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles–mumps–rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3–5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination.

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Section: Discussionsupporting

confidence: 88%

Delayed adaptive immunity is related to higher MMR vaccine‐induced antibody titers in children

et al. 2016

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“…Opposed to our results regarding DTP vaccine responses and immune maturation, it has been shown that a more immature/naïve immune system was related to higher vaccine-specific antibody levels against yellow fever, that is, YF17D a live-attenuated virus vaccine. 34 Young healthy adults in Switzerland responded with higher YF17Dinduced antibody titers compared with vaccinees in Uganda, and the former group presented with lower proportions of memory T-cell subsets and higher fractions of naïve B cells before immunization. 34 The reasons for these differences are still poorly understood.…”

Section: Immune Maturation and Dtp Vaccine Responses A Strömbeck Et Almentioning

confidence: 96%

Earlier infantile immune maturation is related to higher DTP vaccine responses in children

et al. 2016

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There are large inter-individual variations in vaccine-specific antibody responses in children. We sought to investigate whether early-life environmental factors and/or adaptive immune maturation were related to diphtheria–tetanus–pertussis (DTP) vaccine-specific antibody levels at 18 months of age. In the prospective FARMFLORA birth-cohort, including both farming and non-farming families, children were immunized with DTP vaccine at 3, 5 and 12 months of age. DTP vaccine-induced antibody levels were measured in plasma at 18 months of age. Infants' blood samples obtained at birth, 3–5 days, 4, 18 and 36 months and at 8 years of age were analyzed for total CD4+ T- and B-cell counts, proportions of naïve and memory T and B cells, and fractions of putative regulatory T cells by flow cytometry. Multivariate factor analysis was used to examine associations between immune variables and vaccine responses. The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood. Furthermore, lower infantile total T- and B-cell blood counts were associated with higher proportions of circulating CD45RO+ memory T cells and to lower proportions of α4β7+ naïve T cells later in childhood. The multivariate findings were corroborated in univariate correlation analyses. Sex, delivery mode and dairy farm exposure were unrelated to the magnitude of DTP-specific antibody responses. Our results thus suggest that children with a more mature/activated infantile adaptive immunity respond with higher vaccine-induced anti-DTP antibody levels at 18 months of age.

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“…Another potential strategy to enhance the response to vaccines may be to modulate baseline immune status before vaccination with drug administration. Recent human studies have shown that immune activation before vaccination negatively correlates with the response to yellow fever 17D vaccine (28). Additional approaches to enhance vaccine immunity include inhibition or depletion of regulatory immune cells such as myeloid-derived suppressor cells and regulatory T cells, interference with metabolic pathways such as mTOR (mammalian target of rapamycin), and modulation of the microbiome to induce an environment more favorable to vaccine response.…”

Section: Introductionmentioning

confidence: 99%

Developing vaccines for an aging population

2015

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The demographics of the world's population are changing, with many adults now surviving into their 80s. With this change comes the need to protect the aging and other underserved populations not only against infectious diseases but also against cancer and other chronic conditions. New technologies derived from recent advances in the fields of immunology, structural biology, synthetic biology, and genomics have brought a revolution in the vaccine field. Among them, vaccine adjuvants have the potential to harness the immune system to provide protection against new types of diseases, improve protection in young children, and expand this protection to adults and the elderly. However, in order to do so we need also to overcome the nontechnical challenges that could limit the implementation of innovative vaccines, including controversies regarding the safety of adjuvants, increasing regulatory complexity, the inadequate methods used to assess the value of novel vaccines, and the resulting industry alienation from future investment. This Perspective summarizes the outcome of a recent multidisciplinary symposium entitled "Enhancing Vaccine Immunity and Value," held in Siena, Italy, in July 2014, that addressed two related questions: how to improve vaccine efficacy by using breakthrough technologies and how to capture the full potential of novel vaccines.

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Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Cited by 44 publications

References 23 publications

Delayed adaptive immunity is related to higher MMR vaccine‐induced antibody titers in children

Delayed adaptive immunity is related to higher MMR vaccine‐induced antibody titers in children

Earlier infantile immune maturation is related to higher DTP vaccine responses in children

Developing vaccines for an aging population

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