Humoral immune responses to <i>Plasmodium falciparum</i> among HIV‐1‐infected Kenyan adults

Nnedu, Obinna N.; O’Leary, Michael P.; Mutua, Daniel; Mutai, Beth; Kalantari-Dehaghi, Mina; Jasinskas, Al; Nakajima-Sasaki, Rie; John‐Stewart, Grace; Otieno, Phelgona; Liang, Xinmiao; Waitumbi, John N.; Kimani, Francis; Camerini, David; Felgner, Philip L.; Walson, Judd L.; Vigil, Adam

doi:10.1002/prca.201100021

Cited by 22 publications

(14 citation statements)

References 52 publications

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“…Construction of the P. falciparum protein arrays and analysis of Ab binding have been described in detail [10][11][12][13]. Briefly, protein microarrays were constructed by polymerase chain reaction amplification of each complete or partial open reading frame followed by in vivo recombination cloning and in vitro transcription/translation to generate malaria polypeptides used for microarray chip printing.…”

Section: Protein Microarrays and Ab Profilesmentioning

confidence: 99%

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Dent¹,

Nakajima²,

Liang³

et al. 2015

J Infect Dis.

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Background. Immunoglobulin G antibodies (Abs) to Plasmodium falciparum antigens have been associated with naturally acquired immunity to symptomatic malaria.Methods. We probed protein microarrays covering 824 unique P. falciparum protein features with plasma from residents of a community in Kenya monitored for 12 weeks for (re)infection and symptomatic malaria after administration of antimalarial drugs. P. falciparum proteins recognized by Abs from 88 children (aged 1-14 years) and 86 adults (aged ≥18 years), measured at the beginning of the observation period, were ranked by Ab signal intensity.Results. Abs from immune adults reacted with a total 163 of 824 P. falciparum proteins. Children gradually acquired Abs to the full repertoire of antigens recognized by adults. Abs to some antigens showed high seroconversion rates, reaching maximal levels early in childhood, whereas others did not reach adult levels until adolescence. No correlation between Ab signal intensity and time to (re)infection was observed. In contrast, Ab levels to 106 antigens were significantly higher in children who were protected from symptomatic malaria compared with those who were not. Abs to antigens predictive of protection included P. falciparum erythrocyte membrane protein 1, merozoite surface protein (MSP) 10, MSP2, liver-stage antigen 3, PF70, MSP7, and Plasmodium helical interspersed subtelomeric domain protein.Conclusions. Protein microarrays may be useful in the search for malaria antigens associated with protective immunity.

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Section: Protein Microarrays and Ab Profilesmentioning

confidence: 99%

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Dent¹,

Nakajima²,

Liang³

et al. 2015

J Infect Dis.

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“…On the other hand, standard criteria for array production and data normalization with noise models, variance esti-mation, and differential expression analysis techniques have become powerful tools for the interpretation of results. Based on this progress, successful attempts have been made using protein microarrays for profiling the antibody responses to numerous infectious pathogens (3,21,40,54,66).…”

Section: Fig 4 Intensities Of Antibody Responses Against Four Immunodmentioning

confidence: 99%

Immunodominant “Asymptomatic” Herpes Simplex Virus 1 and 2 Protein Antigens Identified by Probing Whole-ORFome Microarrays with Serum Antibodies from Seropositive Asymptomatic versus Symptomatic Individuals

Dasgupta

Chentoufi

Kalantari

et al. 2012

J Virol

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cHerpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant "symptomatic" antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n ‫؍‬ 10) and asymptomatic (n ‫؍‬ 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1-and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients (P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag (P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient "asymptomatic" vaccine against ocular, orofacial, and genital herpes.

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“…It is unclear whether increased malaria vulnerability in HIV is the result of alterations in the B cell response to malaria. Some reports have suggested HIV infection has no effect on malaria Ab production (15), whereas others have found a decrease in the breadth of malaria Ag reactivity (16). Assessment of P. falciparum Ag-specific memory B cells has typically been performed with B cell ELISpots, which allow for some assessment of the Ag-specific memory B cell population.…”

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Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum–Specific Atypical Memory B Cells

Frosch

Odumade

et al. 2017

The Journal of Immunology

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Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels. HIV-infected individuals had a higher proportion of total atypical and total activated memory B cells (MBCs). Using an AMA1 tetramer to detect AMA1-specific B cells, HIV-infected individuals were also shown to have a higher proportion of AMA1-specific atypical MBCs. However, this proportional increase resulted in large part from a loss in the number of naive and resting MBCs rather than an increase in the number of atypical and activated cells. The loss of resting MBCs and naive B cells was mirrored in a population of cells specific for an Ag to which these individuals were unlikely to have been chronically exposed. Together, the data show that changes in Ag-specific B cell subsets in HIV-infected individuals mirror those in the overall B cell population, and suggest that the increased proportion of atypical MBC phenotypes found in HIV-1-infected individuals results from the loss of naive and resting MBCs.

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Humoral immune responses to Plasmodium falciparum among HIV‐1‐infected Kenyan adults

Cited by 22 publications

References 52 publications

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Plasmodium falciparumProtein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya

Immunodominant “Asymptomatic” Herpes Simplex Virus 1 and 2 Protein Antigens Identified by Probing Whole-ORFome Microarrays with Serum Antibodies from Seropositive Asymptomatic versus Symptomatic Individuals

Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum–Specific Atypical Memory B Cells

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