Andrew J Dunning, C. Diazgranados, T. Voloshen, Branda Hu, V. Landolfi, H. Talbot
{"title":"Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial","authors":"Andrew J Dunning, C. Diazgranados, T. Voloshen, Branda Hu, V. Landolfi, H. Talbot","doi":"10.1128/CVI.00604-15","DOIUrl":"https://doi.org/10.1128/CVI.00604-15","url":null,"abstract":"ABSTRACT Although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays. For the hemagglutination inhibition assay, a titer of 40 was found to correspond with 50% protection when the assay virus was antigenically well matched to the circulating virus—the same titer as is generally recognized for 50% protection in younger adults. A dramatically higher titer was required for 50% protection when the assay virus was a poor match to the circulating virus. With the well-matched virus, some protection was seen at the lowest titers; with the poorly matched virus, high levels of protection were not achieved even at the highest titers. Strong associations were also seen between virus neutralization test titers and protection, but reliable estimates for 50% protection were not obtained. An association was seen between titers of an enzyme-linked lectin assay for antineuraminidase N2 antibodies and protection; in particular, the proportion of treatment effect explained by assay titer in models that included both this assay and one of the other assays was consistently higher than in models that included either assay alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01427309.)","PeriodicalId":169862,"journal":{"name":"Clinical and Vaccine Immunology : CVI","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123386433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Dent, I. Malhotra, Xuelie Wang, D. Babineau, K. T. Yeo, Timothy Anderson, Rhonda J. Kimmel, E. Angov, D. Lanar, D. Narum, S. Dutta, J. Richards, J. Beeson, B. Crabb, A. Cowman, T. Horii, E. Muchiri, P. Mungai, C. King, J. Kazura
{"title":"Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort","authors":"A. Dent, I. Malhotra, Xuelie Wang, D. Babineau, K. T. Yeo, Timothy Anderson, Rhonda J. Kimmel, E. Angov, D. Lanar, D. Narum, S. Dutta, J. Richards, J. Beeson, B. Crabb, A. Cowman, T. Horii, E. Muchiri, P. Mungai, C. King, J. Kazura","doi":"10.1128/CVI.00452-15","DOIUrl":"https://doi.org/10.1128/CVI.00452-15","url":null,"abstract":"ABSTRACT IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.","PeriodicalId":169862,"journal":{"name":"Clinical and Vaccine Immunology : CVI","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131383528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stuart D. Blacksell, A. Tanganuchitcharnchai, P. Nawtaisong, P. Kantipong, Achara Laongnualpanich, N. P. Day, Daniel H. Paris
{"title":"Diagnostic Accuracy of the InBios Scrub Typhus Detect Enzyme-Linked Immunoassay for the Detection of IgM Antibodies in Northern Thailand","authors":"Stuart D. Blacksell, A. Tanganuchitcharnchai, P. Nawtaisong, P. Kantipong, Achara Laongnualpanich, N. P. Day, Daniel H. Paris","doi":"10.1128/CVI.00553-15","DOIUrl":"https://doi.org/10.1128/CVI.00553-15","url":null,"abstract":"ABSTRACT In this study, we examined the diagnostic accuracy of the InBios Scrub Typhus Detect IgM enzyme-linked immunosorbent assay (ELISA) and determined the optimal diagnostic optical density (OD) cutoffs for screening and diagnostic applications based on prospectively collected, characterized samples from undifferentiated febrile illness patients in northern Thailand. Direct comparisons with the serological gold standard, indirect immunofluorescence assay (IFA), revealed strong statistical correlation of ELISA OD values and IFA IgM titers. Determination of the optimal ELISA cutoff for seroepidemiology or screening purposes compared to the corresponding IFA reciprocal titer of 400 as previously described for Thailand was 0.60 OD, which corresponded to a sensitivity (Sn) of 84% and a specificity (Sp) of 98%. The diagnostic performance against the improved and more-stringent scrub typhus infection criteria (STIC), correcting for low false-positive IFA titers, resulted in an Sn of 93% and an Sp of 91% at an ELISA cutoff of 0.5 OD. This diagnostic ELISA cutoff corresponds to IFA reciprocal titers of 1,600 to 3,200, which greatly reduces the false-positive rates associated with low-positive IFA titers. These data are in congruence with the recently improved serodiagnostic positivity criteria using the Bayesian latent class modeling approach. In summary, the InBios Scrub Typhus Detect IgM ELISA is affordable and easy-to-use, with adequate diagnostic accuracy for screening and diagnostic purposes, and should be considered an improved alternative to the gold standard IFA for acute diagnosis. For broader application, regional cutoff validation and antigenic composition for consistent diagnostic accuracy should be considered.","PeriodicalId":169862,"journal":{"name":"Clinical and Vaccine Immunology : CVI","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115979535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rhea J. Longley, A. Reyes‐Sandoval, Eduardo Montoya-Diaz, Susanna Dunachie, Chalermpon Kumpitak, W. Nguitragool, I. Mueller, J. Sattabongkot
{"title":"Acquisition and Longevity of Antibodies to Plasmodium vivax Preerythrocytic Antigens in Western Thailand","authors":"Rhea J. Longley, A. Reyes‐Sandoval, Eduardo Montoya-Diaz, Susanna Dunachie, Chalermpon Kumpitak, W. Nguitragool, I. Mueller, J. Sattabongkot","doi":"10.1128/CVI.00501-15","DOIUrl":"https://doi.org/10.1128/CVI.00501-15","url":null,"abstract":"ABSTRACT Plasmodium vivax is now the dominant Plasmodium species causing malaria in Thailand, yet little is known about naturally acquired immune responses to this parasite in this low-transmission region. The preerythrocytic stage of the P. vivax life cycle is considered an excellent target for a malaria vaccine, and in this study, we assessed the stability of the seropositivity and the magnitude of IgG responses to three different preerythrocytic P. vivax proteins in two groups of adults from a region of western Thailand where malaria is endemic. These individuals were enrolled in a yearlong cohort study, which comprised one group that remained P. vivax free (by quantitative PCR [qPCR] detection, n = 31) and another that experienced two or more blood-stage P. vivax infections during the year of follow up (n = 31). Despite overall low levels of seropositivity, IgG positivity and magnitude were long-lived over the 1-year period in the absence of qPCR-detectable blood-stage P. vivax infections. In contrast, in the adults with two or more P. vivax infections during the year, IgG positivity was maintained, but the magnitude of the response to P. vivax circumsporozoite protein 210 (CSP210) decreased over time. These findings demonstrate that long-term humoral immunity can develop in low-transmission regions.","PeriodicalId":169862,"journal":{"name":"Clinical and Vaccine Immunology : CVI","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121631081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Mandala, C. Msefula, E. Gondwe, J. Gilchrist, S. Graham, P. Pensulo, Grace Mwimaniwa, Meraby Banda, T. Taylor, E. Molyneux, M. Drayson, S. Ward, M. Molyneux, C. MacLennan
{"title":"Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria","authors":"W. Mandala, C. Msefula, E. Gondwe, J. Gilchrist, S. Graham, P. Pensulo, Grace Mwimaniwa, Meraby Banda, T. Taylor, E. Molyneux, M. Drayson, S. Ward, M. Molyneux, C. MacLennan","doi":"10.1128/CVI.00564-15","DOIUrl":"https://doi.org/10.1128/CVI.00564-15","url":null,"abstract":"ABSTRACT Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69+ NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4+ lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.","PeriodicalId":169862,"journal":{"name":"Clinical and Vaccine Immunology : CVI","volume":"151 11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131017973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}