Cellular Immunity in Breast Milk: Implications for Postnatal Transmission of HIV-1 to the Infant

  • Steffanie Sabbaj
  • Chris C. Ibegbu
  • Athena P. Kourtis
Chapter

Abstract

Breastfeeding accounts for up to 40% of all infant human immunodeficiency virus (HIV) type 1 infections in resource-limited settings, where prolonged breastfeeding is the only available and safe infant feeding option [1, 2]. However, most breastfed infants remain uninfected even after prolonged exposure to breast milk [3–5]. The factors in breast milk that protect the majority of breastfed infants of HIV-infected mothers from infection remain largely undetermined. Breast milk contains a multitude of immune parameters, including immunoglobulins, antimicrobial substances, pro-and anti-inflammatory cytokines, and leukocytes [6]. Moreover, breast milk not only provides passive protection, but also can directly modulate the immunological development of the infant [7, 8]. Cell-mediated immunity in breast milk has not been as extensively studied as humoral immunity, described in Chap. 10. There is, however, increasing interest in the role that lymphocytes, macrophages, and other immune cell types play, both in innate and in adaptive breast milk immunity [3].

References

  1. 1.
    Kourtis AP, Bulterys M (2010) Mother-to-child transmission of HIV: pathogenesis, mechanisms and pathways. Clin Perinatol 37(4):721–737PubMedCrossRefGoogle Scholar
  2. 2.
    Kourtis AP, Butera S, Ibegbu C, Beled L, Duerr A (2003) Breast milk and HIV-1: vector of transmission or vehicle of protection? Lancet Infect Dis 3(12):786–793PubMedCrossRefGoogle Scholar
  3. 3.
    Aldrovandi GM, Kuhn L (2010) What infants and breasts can teach us about natural protection from HIV infection. J Infect Dis 202(Suppl 3):S366–S370Google Scholar
  4. 4.
    Leroy V, Newell ML, Dabis F, Peckham C, Van de Perre P, Bulterys M et al (1998) International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Ghent International Working Group on Mother-to-Child Transmission of HIV. Lancet 352(9128):597–600PubMedCrossRefGoogle Scholar
  5. 5.
    Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J, Mwatha A et al (2000) Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 283(9):1167–1174PubMedCrossRefGoogle Scholar
  6. 6.
    Van de Perre P, Simonon A, Hitimana DG, Dabis F, Msellati P, Mukamabano B et al (1993) Infective and anti-infective properties of breastmilk from HIV-1-infected women. Lancet 341(8850):914–918PubMedCrossRefGoogle Scholar
  7. 7.
    Garofalo R (2010) Cytokines in human milk. J Pediatr 156(2 Suppl):S36–S40Google Scholar
  8. 8.
    Goldman AS, Chheda S, Garofalo R, Schmalstieg FC (1996) Cytokines in human milk: properties and potential effects upon the mammary gland and the neonate. J Mammary Gland Biol Neoplasia 1(3):251–258PubMedCrossRefGoogle Scholar
  9. 9.
    Koulinska IN, Villamor E, Chaplin B, Msamanga G, Fawzi W, Renjifo B et al (2006) Transmission of cell-free and cell-associated HIV-1 through breast-feeding. J Acquir Immune Defic Syndr 41(1):93–99PubMedCrossRefGoogle Scholar
  10. 10.
    Rousseau CM, Nduati RW, Richardson BA, Steele MS, John-Stewart GC, Mbori-Ngacha DA et al (2003) Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis 187(5):741–747PubMedCrossRefGoogle Scholar
  11. 11.
    Toniolo A, Serra C, Conaldi PG, Basolo F, Falcone V, Dolei A (1995) Productive HIV-1 infection of normal human mammary epithelial cells. AIDS 9(8):859–866PubMedCrossRefGoogle Scholar
  12. 12.
    Alfsen A, Yu H, Magerus-Chatinet A, Schmitt A, Bomsel M (2005) HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer. Mol Biol Cell 16(9):4267–4279PubMedCrossRefGoogle Scholar
  13. 13.
    Bulek K, Swaidani S, Aronica M, Li X (2010) Epithelium: the interplay between innate and Th2 immunity. Immunol Cell Biol 88(3):257–268PubMedCrossRefGoogle Scholar
  14. 14.
    Dorosko SM, Connor RI (2010) Primary human mammary epithelial cells endocytose HIV-1 and facilitate viral infection of CD4+ T lymphocytes. J Virol 84(20):10533–10542PubMedCrossRefGoogle Scholar
  15. 15.
    Lyimo MA, Howell AL, Balandya E, Eszterhas SK, Connor RI (2009) Innate factors in human breast milk inhibit cell-free HIV-1 but not cell-associated HIV-1 infection of CD4+ cells. J Acquir Immune Defic Syndr 51(2):117–124PubMedCrossRefGoogle Scholar
  16. 16.
    Bertotto A, Castellucci G, Radicioni M, Bartolucci M, Vaccaro R (1996) CD40 ligand expression on the surface of colostral T cells. Arch Dis Child Fetal Neonatal Ed 74(2):F135–F136PubMedCrossRefGoogle Scholar
  17. 17.
    Bertotto A, Gerli R, Fabietti G, Crupi S, Arcangeli C, Scalise F et al (1990) Human breast milk T lymphocytes display the phenotype and functional characteristics of memory T cells. Eur J Immunol 20(8):1877–1880PubMedCrossRefGoogle Scholar
  18. 18.
    Bertotto A, Spinozzi F, Gerli R, Castellucci G, Bassotti G, Crupi S et al (1995) CD26 and CD31 surface antigen expression on human colostral T cells. Biol Neonate 68(4):259–263PubMedCrossRefGoogle Scholar
  19. 19.
    Crago SS, Prince SJ, Pretlow TG, McGhee JR, Mestecky J (1979) Human colostral cells. I. Separation and characterization. Clin Exp Immunol 38(3):585–597PubMedGoogle Scholar
  20. 20.
    Davis MK (1991) Human milk and HIV infection: epidemiologic and laboratory data. Adv Exp Med Biol 310:271–280PubMedCrossRefGoogle Scholar
  21. 21.
    Eglinton BA, Roberton DM, Cummins AG (1994) Phenotype of T cells, their soluble receptor levels, and cytokine profile of human breast milk. Immunol Cell Biol 72(4):306–313PubMedCrossRefGoogle Scholar
  22. 22.
    Goldman AS, Chheda S, Garofalo R (1998) Evolution of immunologic functions of the mammary gland and the postnatal development of immunity. Pediatr Res 43(2):155–162PubMedCrossRefGoogle Scholar
  23. 23.
    Jarvinen KM, Suomalainen H (2002) Leucocytes in human milk and lymphocyte subsets in cow’s milk-allergic infants. Pediatr Allergy Immunol 13(4):243–254PubMedCrossRefGoogle Scholar
  24. 24.
    Lindstrand A, Smedman L, Gunnlaugsson G, Troye-Blomberg M (1997) Selective compartmentalization of gammadelta-T lymphocytes in human breastmilk. Acta Paediatr 86(8):890–891PubMedCrossRefGoogle Scholar
  25. 25.
    Moro I, Abo T, Crago SS, Komiyama K, Mestecky J (1985) Natural killer cells in human colostrum. Cell Immunol 93(2):467–474PubMedCrossRefGoogle Scholar
  26. 26.
    Ogra SS, Ogra PL (1978) Immunologic aspects of human colostrum and milk. II. Characteristics of lymphocyte reactivity and distribution of E-rosette forming cells at different times after the onset of lactation. J Pediatr 92(4):550–555PubMedCrossRefGoogle Scholar
  27. 27.
    Ogra SS, Weintraub D, Ogra PL (1977) Immunologic aspects of human colostrum and milk. III. Fate and absorption of cellular and soluble components in the gastrointestinal tract of the newborn. J Immunol 119(1):245–248PubMedGoogle Scholar
  28. 28.
    Xanthou M (1997) Human milk cells. Acta Paediatr 86(12):1288–1290PubMedCrossRefGoogle Scholar
  29. 29.
    Parmely MJ, Beer AE, Billingham RE (1976) In vitro studies on the T-lymphocyte population of human milk. J Exp Med 144(2):358–370PubMedCrossRefGoogle Scholar
  30. 30.
    Thorpe LW, Rudloff HE, Powell LC, Goldman AS (1986) Decreased response of human milk leukocytes to chemoattractant peptides. Pediatr Res 20(4):373–377PubMedCrossRefGoogle Scholar
  31. 31.
    Williamson MT, Murti PK (1996) Effects of storage, time, temperature, and composition of containers on biologic components of human milk. J Hum Lact 12(1):31–35PubMedCrossRefGoogle Scholar
  32. 32.
    Ho FC, Wong RL, Lawton JW (1979) Human colostral and breast milk cells. A light and electron microscopic study. Acta Paediatr Scand 68(3):389–396PubMedCrossRefGoogle Scholar
  33. 33.
    Keller MA, Turner JL, Stratton JA, Miller ME (1980) Breast milk lymphocyte response to K1 antigen of Escherichia coli. Infect Immun 27(3):903–909PubMedGoogle Scholar
  34. 34.
    Wirt DP, Adkins LT, Palkowetz KH, Schmalstieg FC, Goldman AS (1992) Activated and memory T lymphocytes in human milk. Cytometry 13(3):282–290PubMedCrossRefGoogle Scholar
  35. 35.
    Satomi M, Shimizu M, Shinya E, Watari E, Owaki A, Hidaka C et al (2005) Transmission of macrophage-tropic HIV-1 by breast-milk macrophages via DC-SIGN. J Infect Dis 191(2):174–181PubMedCrossRefGoogle Scholar
  36. 36.
    Yagi Y, Watanabe E, Watari E, Shinya E, Satomi M, Takeshita T et al (2010) Inhibition of DC-SIGN-mediated transmission of human immunodeficiency virus type 1 by Toll-like receptor 3 signalling in breast milk macrophages. Immunology 130(4):597–607PubMedCrossRefGoogle Scholar
  37. 37.
    Kourtis AP, Ibegbu CC, Theiler R, Xu YX, Bansil P, Jamieson DJ et al (2007) Breast milk CD4+ T cells express high levels of C chemokine receptor 5 and CXC chemokine receptor 4 and are preserved in HIV-infected mothers receiving highly active antiretroviral therapy. J Infect Dis 195(7):965–972PubMedCrossRefGoogle Scholar
  38. 38.
    Tuaillon E, Valea D, Becquart P, Al Tabaa Y, Meda N, Bollore K et al (2009) Human milk-derived B cells: a highly activated switched memory cell population primed to secrete antibodies. J Immunol 182(11):7155–7162PubMedCrossRefGoogle Scholar
  39. 39.
    Ichikawa M, Sugita M, Takahashi M, Satomi M, Takeshita T, Araki T et al (2003) Breast milk macrophages spontaneously produce granulocyte–macrophage colony-stimulating factor and differentiate into dendritic cells in the presence of exogenous interleukin-4 alone. Immunology 108(2):189–195PubMedCrossRefGoogle Scholar
  40. 40.
    Sabbaj S, Ghosh MK, Edwards BH, Leeth R, Decker WD, Goepfert PA et al (2005) Breast milk-derived antigen-specific CD8+ T cells: an extralymphoid effector memory cell population in humans. J Immunol 174(5):2951–2956PubMedGoogle Scholar
  41. 41.
    Rivas RA, el-Mohandes AA, Katona IM (1994) Mononuclear phagocytic cells in human milk: HLA-DR and Fc gamma R ligand expression. Biol Neonate 66(4):195–204PubMedCrossRefGoogle Scholar
  42. 42.
    Farstad IN, Halstensen TS, Lien B, Kilshaw PJ, Lazarovits AI, Brandtzaeg P (1996) Distribution of beta 7 integrins in human intestinal mucosa and organized gut-associated lymphoid tissue. Immunology 89(2):227–237PubMedCrossRefGoogle Scholar
  43. 43.
    Hladik F, Lentz G, Delpit E, McElroy A, McElrath MJ (1999) Coexpression of CCR5 and IL-2 in human genital but not blood T cells: implications for the ontogeny of the CCR5+ Th1 phenotype. J Immunol 163(4):2306–2313PubMedGoogle Scholar
  44. 44.
    Hussain LA, Kelly CG, Fellowes R, Hecht EM, Wilson J, Chapman M et al (1992) Expression and gene transcript of Fc receptors for IgG, HLA class II antigens and Langerhans cells in human cervico-vaginal epithelium. Clin Exp Immunol 90(3):530–538PubMedCrossRefGoogle Scholar
  45. 45.
    Johansson EL, Rudin A, Wassen L, Holmgren J (1999) Distribution of lymphocytes and adhesion molecules in human cervix and vagina. Immunology 96(2):272–277PubMedCrossRefGoogle Scholar
  46. 46.
    Quayle AJ, Kourtis AP, Cu-Uvin S, Politch JA, Yang H, Bowman FP et al (2007) T-lymphocyte profile and total and virus-specific immunoglobulin concentrations in the cervix of HIV-1-infected women. J Acquir Immune Defic Syndr 44(3):292–298PubMedCrossRefGoogle Scholar
  47. 47.
    Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL et al (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280(5362):427–431PubMedCrossRefGoogle Scholar
  48. 48.
    Zabel BA, Agace WW, Campbell JJ, Heath HM, Parent D, Roberts AI et al (1999) Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J Exp Med 190(9):1241–1256PubMedCrossRefGoogle Scholar
  49. 49.
    Bush JF, Beer AE (1979) Analysis of complement receptors on B-lymphocytes in human milk. Am J Obstet Gynecol 133(6):708–712PubMedGoogle Scholar
  50. 50.
    Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ et al (2004) CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200(6):749–759PubMedCrossRefGoogle Scholar
  51. 51.
    Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M (2005) Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434(7037):1093–1097PubMedCrossRefGoogle Scholar
  52. 52.
    Permar SR, Kang HH, Carville A, Wilks AB, Mansfield KG, Rao SS et al (2010) Preservation of memory CD4(+) T lymphocytes in breast milk of lactating rhesus monkeys during acute simian immunodeficiency virus infection. J Infect Dis 201(2):302–310Google Scholar
  53. 53.
    Alkhatib G (2009) The biology of CCR5 and CXCR4. Curr Opin HIV AIDS 4(2):96–103PubMedCrossRefGoogle Scholar
  54. 54.
    Wu Y, Yoder A (2009) Chemokine coreceptor signaling in HIV-1 infection and pathogenesis. PLoS Pathog 5(12):e1000520PubMedCrossRefGoogle Scholar
  55. 55.
    Veazey RS, Marx PA, Lackner AA (2003) Vaginal CD4+ T cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J Infect Dis 187(5):769–776PubMedCrossRefGoogle Scholar
  56. 56.
    Petitjean G, Becquart P, Tuaillon E, Al Tabaa Y, Valea D, Huguet MF et al (2007) Isolation and characterization of HIV-1-infected resting CD4+ T lymphocytes in breast milk. J Clin Virol 39(1):1–8PubMedCrossRefGoogle Scholar
  57. 57.
    Brenchley JM, Karandikar NJ, Betts MR, Ambrozak DR, Hill BJ, Crotty LE et al (2003) Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 101(7):2711–2720PubMedCrossRefGoogle Scholar
  58. 58.
    Lewis P, Nduati R, Kreiss JK, John GC, Richardson BA, Mbori-Ngacha D et al (1998) Cell-free human immunodeficiency virus type 1 in breast milk. J Infect Dis 177(1):34–39PubMedCrossRefGoogle Scholar
  59. 59.
    Smith CW, Goldman AS (1968) The cells of human colostrum. I. In vitro studies of morphology and functions. Pediatr Res 2(2):103–109PubMedCrossRefGoogle Scholar
  60. 60.
    Allison JP, McIntyre BW, Bloch D (1982) Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol 129(5):2293–2300PubMedGoogle Scholar
  61. 61.
    Haskins K, Kubo R, White J, Pigeon M, Kappler J, Marrack P (1983) The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med 157(4):1149–1169PubMedCrossRefGoogle Scholar
  62. 62.
    Hedrick SM, Cohen DI, Nielsen EA, Davis MM (1984) Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308(5955):149–153PubMedCrossRefGoogle Scholar
  63. 63.
    Hedrick SM, Nielsen EA, Kavaler J, Cohen DI, Davis MM (1984) Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature 308(5955):153–158PubMedCrossRefGoogle Scholar
  64. 64.
    Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL (1983) Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med 157(2):705–719PubMedCrossRefGoogle Scholar
  65. 65.
    Yanagi Y, Yoshikai Y, Leggett K, Clark SP, Aleksander I, Mak TW (1984) A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308(5955):145–149PubMedCrossRefGoogle Scholar
  66. 66.
    Ruben FL, Holzman IR, Fireman P (1982) Responses of lymphocytes from human colostrum or milk to influenza antigens. Am J Obstet Gynecol 143(5):518–522PubMedGoogle Scholar
  67. 67.
    Totterdell BM, Patel S, Banatvala JE, Chrystie IL (1988) Development of a lymphocyte transformation assay for rotavirus in whole blood and breast milk. J Med Virol 25(1):27–36PubMedCrossRefGoogle Scholar
  68. 68.
    Scott R, Scott M, Toms GL (1985) Cellular reactivity to respiratory syncytial virus in human colostrum and breast milk. J Med Virol 17(1):83–93PubMedCrossRefGoogle Scholar
  69. 69.
    Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB (1994) Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68(9):6103–6110PubMedGoogle Scholar
  70. 70.
    Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W et al (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68(7):4650–4655PubMedGoogle Scholar
  71. 71.
    Carrington M, Nelson GW, Martin MP, Kissner T, Vlahov D, Goedert JJ et al (1999) HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283(5408):1748–1752PubMedCrossRefGoogle Scholar
  72. 72.
    Hendel H, Caillat-Zucman S, Lebuanec H, Carrington M, O’Brien S, Andrieu JM et al (1999) New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS. J Immunol 162(11):6942–6946PubMedGoogle Scholar
  73. 73.
    Kaslow RA, Carrington M, Apple R, Park L, Munoz A, Saah AJ et al (1996) Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 2(4):405–411PubMedCrossRefGoogle Scholar
  74. 74.
    Keet IP, Tang J, Klein MR, LeBlanc S, Enger C, Rivers C et al (1999) Consistent associations of HLA class I and II and transporter gene products with progression of human immunodeficiency virus type 1 infection in homosexual men. J Infect Dis 180(2):299–309PubMedCrossRefGoogle Scholar
  75. 75.
    Nelson GW, Kaslow R, Mann DL (1997) Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele’s association with relative rates of disease progression after HIV-1 infection. Proc Natl Acad Sci USA 94(18):9802–9807PubMedCrossRefGoogle Scholar
  76. 76.
    Lohman BL, Slyker J, Mbori-Ngacha D, Bosire R, Farquhar C, Obimbo E et al (2003) Prevalence and magnitude of human immunodeficiency virus (HIV) type 1-specific lymphocyte responses in breast milk from HIV-1-seropositive women. J Infect Dis 188(11):1666–1674PubMedCrossRefGoogle Scholar
  77. 77.
    Sabbaj S, Edwards BH, Ghosh MK, Semrau K, Cheelo S, Thea DM et al (2002) Human immunodeficiency virus-specific CD8(+) T cells in human breast milk. J Virol 76(15):7365–7373PubMedCrossRefGoogle Scholar
  78. 78.
    Diaz-Jouanen E, Williams RC Jr (1974) T and B lymphocytes in human colostrum. Clin Immunol Immunopathol 3(2):248–255PubMedCrossRefGoogle Scholar
  79. 79.
    Becquart P, Chomont N, Roques P, Ayouba A, Kazatchkine MD, Belec L et al (2002) Compartmentalization of HIV-1 between breast milk and blood of HIV-infected mothers. Virology 300(1):109–117PubMedCrossRefGoogle Scholar
  80. 80.
    Losonsky GA, Fishaut JM, Strussenberg J, Ogra PL (1982) Effect of immunization against rubella on lactation products. I. Development and characterization of specific immunologic reactivity in breast milk. J Infect Dis 145(5):654–660PubMedCrossRefGoogle Scholar
  81. 81.
    Permar SR, Kang HH, Carville A, Mansfield KG, Gelman RS, Rao SS et al (2008) Potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys. J Immunol 181(5):3643–3650PubMedGoogle Scholar
  82. 82.
    Wilks AB, Christian EC, Seaman MS, Sircar P, Carville A, Gomez CE et al (2010) Robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus DNA prime and live virus vector boost vaccination of lactating rhesus monkeys. J Immunol 185(11):7097–7106Google Scholar
  83. 83.
    Kunkel EJ, Campbell JJ, Haraldsen G, Pan J, Boisvert J, Roberts AI et al (2000) Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med 192(5):761–768PubMedCrossRefGoogle Scholar
  84. 84.
    Jain L, Vidyasagar D, Xanthou M, Ghai V, Shimada S, Blend M (1989) In vivo distribution of human milk leucocytes after ingestion by newborn baboons. Arch Dis Child 64(7 Spec No):930–933Google Scholar
  85. 85.
    Manning LS, Parmely MJ (1980) Cellular determinants of mammary cell-mediated immunity in the rat. I. The migration of radioisotopically labeled T lymphocytes. J Immunol 125(6):2508–2514PubMedGoogle Scholar
  86. 86.
    Schnorr KL, Pearson LD (1984) Intestinal absorption of maternal leucocytes by newborn lambs. J Reprod Immunol 6(5):329–337PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Steffanie Sabbaj
    • 1
  • Chris C. Ibegbu
    • 2
  • Athena P. Kourtis
    • 3
  1. 1.Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Emory Vaccine CenterEmory University School of MedicineAtlantaUSA
  3. 3.Division of Reproductive HealthNCCDPHP, Centers for Disease Control and PreventionAtlantaUSA

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