HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads
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{"title"=>"HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads", "type"=>"journal", "authors"=>[{"first_name"=>"Jennifer", "last_name"=>"Mabuka", "scopus_author_id"=>"8517468700"}, {"first_name"=>"Ruth", "last_name"=>"Nduati", "scopus_author_id"=>"7004229691"}, {"first_name"=>"Katherine", "last_name"=>"Odem-Davis", "scopus_author_id"=>"49561770500"}, {"first_name"=>"Dylan", "last_name"=>"Peterson", "scopus_author_id"=>"56322264800"}, {"first_name"=>"Julie", "last_name"=>"Overbaugh", "scopus_author_id"=>"7005063858"}], "year"=>2012, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537366", "pui"=>"365284274", "pmid"=>"22719248", "isbn"=>"1098-5514 (Electronic)\\n0022-538X (Linking)", "doi"=>"10.1371/journal.ppat.1002739", "sgr"=>"84864055665", "scopus"=>"2-s2.0-84864055665"}, "id"=>"0fd60a33-3c69-3023-95f3-6cbb6874c396", "abstract"=>"There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS)--only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log(10) lower (compared to 0.59 log(10) lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001) and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk.", "link"=>"http://www.mendeley.com/research/hivspecific-antibodies-capable-adcc-common-breastmilk-associated-reduced-risk-transmission-women-hig", "reader_count"=>54, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Librarian"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>4, "Student > Master"=>11, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Librarian"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>4, "Student > Master"=>11, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>10, "Social Sciences"=>5, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Social Sciences"=>{"Social Sciences"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"United Kingdom"=>1, "South Africa"=>2, "Chile"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/624487"], "description"=>"a<p>Plasma neutralization assays were performed at a starting dilution of 1∶100; an IC50 of 50 was assigned in cases where 50% neutralization was not achieved.</p>b<p>BMS neutralization assays were performed at a starting dilution of 1∶20; an IC50 of 10 was assigned in cases where 50% neutralization was not achieved.</p>c<p>Viral Load.</p>d<p>Indicates week since delivery when infant was first HIV-1 DNA positive.</p>e<p>Indicates time-point after delivery at which BM sample was obtained.</p>f<p>Q461.d1.</p>g<p>Not done.</p>h<p>Not applicable.</p>i<p>Below detection.</p>", "links"=>[], "tags"=>["characteristics", "transmitting", "non-transmitting", "women", "neutralization", "ic50s", "plasma"], "article_id"=>294974, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.t001", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_characteristics_of_transmitting_and_non_transmitting_women_in_the_study_and_the_neutralization_IC50s_of_their_plasma_and_BMS_/294974", "title"=>"The characteristics of transmitting and non-transmitting women in the study and the neutralization IC50s of their plasma and BMS.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-14 01:22:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/624374"], "description"=>"<p>The Y-axis shows % ADCC activity in BMS (1∶100) and the X-axis shows the log<sub>10</sub> BM HIV-1 env specific IgG titers. Filled and open symbols represent transmitting and non-transmitting women, respectively. The trend line ‘Linear (ALL)’ is the regression line including both transmitting and non-transmitting women.</p>", "links"=>[], "tags"=>["hiv-1", "env", "igg", "titers"], "article_id"=>294860, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ADCC_activity_in_relation_to_HIV_1_Env_specific_IgG_titers_in_BMS_/294860", "title"=>"ADCC activity in relation to HIV-1 Env specific IgG titers in BMS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:21:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/624429"], "description"=>"<p>(A) Relation of HIV-1 gp140 specific IgG titers and maternal transmission. Results are from duplicate testing of unfractionated BMS and plasma and are an average of at least two independent experiments. The Y-axis shows the log<sub>10</sub> HIV-1 env specific IgG titers (reciprocal dilution) and the X-axis shows the sample type (BMS versus plasma) and HIV transmission status (NT versus T). (B) BMS and plasma mediated ADCC activity in relation to transmission. The Y-axis shows the % ADCC activity and the X-axis shows the sample type and HIV transmission status. In both panels, triangles and circles represent BMS and plasma, respectively while open and filled symbols represented non-transmitting and transmitting women, respectively. Results are from duplicate testing of unfractionated BMS and plasma and are an average of at least two independent experiments.</p>", "links"=>[], "tags"=>["env", "igg", "titers", "adcc", "bms"], "article_id"=>294919, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g007", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIV_1_Env_specific_IgG_titers_and_ADCC_activity_in_BMS_in_relation_to_infant_infection_/294919", "title"=>"HIV-1 Env specific IgG titers and ADCC activity in BMS in relation to infant infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:21:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/324801", "https://ndownloader.figshare.com/files/324832", "https://ndownloader.figshare.com/files/324875", "https://ndownloader.figshare.com/files/324906"], "description"=>"<div><p>There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS) – only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log<sub>10</sub> lower (compared to 0.59 log<sub>10</sub> lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001)and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk.</p> </div>", "links"=>[], "tags"=>["hiv-specific", "antibodies", "adcc", "are", "breastmilk", "reduced", "women", "viral", "loads"], "article_id"=>124098, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002739.s001", "https://dx.doi.org/10.1371/journal.ppat.1002739.s002", "https://dx.doi.org/10.1371/journal.ppat.1002739.s003", "https://dx.doi.org/10.1371/journal.ppat.1002739.s004"], "stats"=>{"downloads"=>14, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/HIV_Specific_Antibodies_Capable_of_ADCC_Are_Common_in_Breastmilk_and_Are_Associated_with_Reduced_Risk_of_Transmission_in_Women_with_High_Viral_Loads/124098", "title"=>"HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-06-14 01:08:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/624036"], "description"=>"<p>The graphs show percent neutralization versus BMS purified IgG (A) or IgA (B) dilution. The corresponding symbol for the data from each of the four mothers is shown in the upper right corner. Neutralization by IgG and IgA is represented by filled and open symbols, respectively. Results using pseudovirus generated with Q461.d1 env (HIV-1 in black lines) are shown in the left graph and with SIVMneCl8 (SIV in grey lines) are shown in the right graph. The 50% neutralization level is shown with a dotted line. The results are from duplicate testing and are representative of at least two independent experiments. The average IC50s for the two experiments for all 19 women is reported in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002739#ppat.1002739.s002\" target=\"_blank\">Table S1</a>.</p>", "links"=>[], "tags"=>["potency", "purified", "igg", "iga", "mothers", "heterologous"], "article_id"=>294525, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_potency_of_purified_IgG_and_IgA_from_four_mothers_against_heterologous_virus_/294525", "title"=>"Neutralization potency of purified IgG and IgA from four mothers against heterologous virus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:15:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/624283"], "description"=>"<p>Percent ADCC activity in BMS(A) and plasma (B). BMS was tested at a 1∶100 dilution and plasma at a 1∶1000 dilution. The subject ID for the corresponding ADCC measure is shown below each bar. The results are from duplicate testing and are an average of at least two independent experiments each done using effector cells from a single donor. nd indicates not done.</p>", "links"=>[], "tags"=>["bms"], "article_id"=>294780, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g005", "stats"=>{"downloads"=>5, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ADCC_activity_in_BMS_and_plasma_/294780", "title"=>"ADCC activity in BMS and plasma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:19:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/624226"], "description"=>"<p>(A)Total IgG and IgA in unfractionated BMS and plasma. The Y-axis shows the log<sub>10</sub> Ab conc (ug/ml) and the X-axis shows the sample type and Ab isotype. Black and grey symbols denote BMS and plasma, respectively. Triangles and circles represent IgG and IgA, respectively. (B) Unfractionated BMS and plasma HIV-1 env specific IgG and IgA titers. The Y-axis shows the log<sub>10</sub> HIV-1 env specific titers (reciprocal dilution) and the X-axis shows the sample type and Ab isotype. Symbols are as described for A.</p>", "links"=>[], "tags"=>["hiv-1", "env", "igg", "iga", "unfractionated", "bms"], "article_id"=>294710, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Levels_of_total_and_HIV_1_env_specific_IgG_and_IgA_in_unfractionated_BMS_and_plasma_/294710", "title"=>"Levels of total and HIV-1 env specific IgG and IgA in unfractionated BMS and plasma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:18:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/623915"], "description"=>"<p>The graphs show percent neutralization versus plasma (A) or BMS (B) dilution. Results using pseudovirus generated with heterologous Q461.d1 env (HIV-1 in black lines) are shown in the left graph and with SIVMneCl8 (SIV in grey lines) are shown in the right graph. The corresponding symbol for the data from each of the four mothers is shown in the upper right corner. The 50% neutralization level is shown with a dotted line. The results are from triplicate testing and are representative of at least two independent experiments. The average IC50s for the two experiments for all 19 women is reported in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002739#ppat-1002739-t001\" target=\"_blank\">Table 1</a>.</p>", "links"=>[], "tags"=>["potency", "plasma", "bms", "mothers", "heterologous"], "article_id"=>294404, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_potency_of_plasma_and_BMS_from_four_mothers_against_heterologous_virus_/294404", "title"=>"Neutralization potency of plasma and BMS from four mothers against heterologous virus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:13:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/624137"], "description"=>"<p>Representative graphs showing percent neutralization versus BMS purified IgG or IgA dilution. (a) Neutralization by IgG and IgA fractions from subject MM471 and (b) neutralization by IgG and IgA fractions from subject MA411. IgG (filled square) and IgA (open square) responses against pseudovirus generated with autologous HIV-1 env are shown in black lines and against SIVMneCl8 (SIV) are shown in grey lines. The 50% neutralization level is shown with a dotted line. The results are from duplicate testing and are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["potency", "igg", "iga", "mothers", "autologous"], "article_id"=>294625, "categories"=>["Immunology"], "users"=>["Jennifer Mabuka", "Ruth Nduati", "Katherine Odem-Davis", "Dylan Peterson", "Julie Overbaugh"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002739.g003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_potency_of_IgG_and_IgA_from_two_mothers_against_autologous_virus_/294625", "title"=>"Neutralization potency of IgG and IgA from two mothers against autologous virus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-14 01:17:05"}

PMC Usage Stats | Further Information

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