Abstract
The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1.
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Selected References
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- Amadori A., De Rossi A., Chieco-Bianchi L., Giaquinto C., De Maria A., Ades A. E. Diagnosis of human immunodeficiency virus 1 infection in infants: in vitro production of virus-specific antibody in lymphocytes. Pediatr Infect Dis J. 1990 Jan;9(1):26–30. doi: 10.1097/00006454-199001000-00006. [DOI] [PubMed] [Google Scholar]
- Amadori A., De Rossi A., Faulkner-Valle G. P., Chieco-Bianchi L. Spontaneous in vitro production of virus-specific antibody by lymphocytes from HIV-infected subjects. Clin Immunol Immunopathol. 1988 Mar;46(3):342–351. doi: 10.1016/0090-1229(88)90053-0. [DOI] [PubMed] [Google Scholar]
- Amadori A., de Rossi A., Giaquinto C., Faulkner-Valle G., Zacchello F., Chieco-Bianchi L. In-vitro production of HIV-specific antibody in children at risk of AIDS. Lancet. 1988 Apr 16;1(8590):852–854. doi: 10.1016/s0140-6736(88)91603-0. [DOI] [PubMed] [Google Scholar]
- Andersson U., Bird A. G., Britton B. S., Palacios R. Humoral and cellular immunity in humans studied at the cell level from birth to two years of age. Immunol Rev. 1981;57:1–38. doi: 10.1111/j.1600-065x.1981.tb00440.x. [DOI] [PubMed] [Google Scholar]
- Borkowsky W., Krasinski K., Moore T., Papaevangelou V. Lymphocyte proliferative responses to HIV-1 envelope and core antigens by infected and uninfected adults and children. AIDS Res Hum Retroviruses. 1990 May;6(5):673–678. doi: 10.1089/aid.1990.6.673. [DOI] [PubMed] [Google Scholar]
- Borkowsky W., Krasinski K., Pollack H., Hoover W., Kaul A., Ilmet-Moore T. Early diagnosis of human immunodeficiency virus infection in children less than 6 months of age: comparison of polymerase chain reaction, culture, and plasma antigen capture techniques. J Infect Dis. 1992 Sep;166(3):616–619. doi: 10.1093/infdis/166.3.616. [DOI] [PubMed] [Google Scholar]
- Courgnaud V., Lauré F., Brossard A., Bignozzi C., Goudeau A., Barin F., Bréchot C. Frequent and early in utero HIV-1 infection. AIDS Res Hum Retroviruses. 1991 Mar;7(3):337–341. doi: 10.1089/aid.1991.7.337. [DOI] [PubMed] [Google Scholar]
- Durandy A., Fischer A., Griscelli C. Active suppression of B lymphocyte maturation by two different newborn T lymphocyte subsets. J Immunol. 1979 Dec;123(6):2644–2650. [PubMed] [Google Scholar]
- Gaetano C., Scano G., Carbonari M., Giannini G., Mezzaroma I., Aiuti F., Marolla L., Casadei A. M., Carapella E. Delayed and defective anti-HIV IgM response in infants. Lancet. 1987 Mar 14;1(8533):631–631. doi: 10.1016/s0140-6736(87)90272-8. [DOI] [PubMed] [Google Scholar]
- Gaines H., von Sydow M., Sönnerborg A., Albert J., Czajkowski J., Pehrson P. O., Chiodi F., Moberg L., Fenyö E. M., Asjö B. Antibody response in primary human immunodeficiency virus infection. Lancet. 1987 May 30;1(8544):1249–1253. doi: 10.1016/s0140-6736(87)92696-1. [DOI] [PubMed] [Google Scholar]
- Gathings W. E., Kubagawa H., Cooper M. D. A distinctive pattern of B cell immaturity in perinatal humans. Immunol Rev. 1981;57:107–126. doi: 10.1111/j.1600-065x.1981.tb00444.x. [DOI] [PubMed] [Google Scholar]
- Gill T. J., 3rd, Repetti C. F., Metlay L. A., Rabin B. S., Taylor F. H., Thompson D. S., Cortese A. L. Transplacental immunization of the human fetus to tetanus by immunization of the mother. J Clin Invest. 1983 Sep;72(3):987–996. doi: 10.1172/JCI111071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goedert J. J., Duliège A. M., Amos C. I., Felton S., Biggar R. J. High risk of HIV-1 infection for first-born twins. The International Registry of HIV-exposed Twins. Lancet. 1991 Dec 14;338(8781):1471–1475. doi: 10.1016/0140-6736(91)92297-f. [DOI] [PubMed] [Google Scholar]
- Grimaldi L. M., Roos R. P., Devare S. G., Robey W. G., Casey J. M., Gurney M. E., Apatoff B. R., Lazzarin D. Restricted heterogeneity of antibody to gp120 and p24 in AIDS. J Immunol. 1988 Jul 1;141(1):114–117. [PubMed] [Google Scholar]
- Hayward A. R., Lawton A. R. Induction of plasma cell differentiation of human fetal lymphocytes: evidence for functional immaturity of T and B cells. J Immunol. 1977 Oct;119(4):1213–1217. [PubMed] [Google Scholar]
- Joller-Jemelka H. I., Joller P. W., Müller F., Schüpbach J., Grob P. J. Anti-HIV IgM antibody analysis during early manifestations of HIV infections. AIDS. 1987 May;1(1):45–47. [PubMed] [Google Scholar]
- Kobayashi R. H., Hyman C. J., Stiehm E. R. Immunologic maturation in an infant born to a mother with agammaglobulinemia. Am J Dis Child. 1980 Oct;134(10):942–944. doi: 10.1001/archpedi.1980.02130220020006. [DOI] [PubMed] [Google Scholar]
- Krivine A., Firtion G., Cao L., Francoual C., Henrion R., Lebon P. HIV replication during the first weeks of life. Lancet. 1992 May 16;339(8803):1187–1189. doi: 10.1016/0140-6736(92)91131-q. [DOI] [PubMed] [Google Scholar]
- Landesman S., Weiblen B., Mendez H., Willoughby A., Goedert J. J., Rubinstein A., Minkoff H., Moroso G., Hoff R. Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection. JAMA. 1991 Dec 25;266(24):3443–3446. [PubMed] [Google Scholar]
- Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
- Laursen H. B., Christensen M. F. Immunoglobulins in normal infant born of severe hypo-gamma-globulinaemic mother. Arch Dis Child. 1973 Aug;48(8):646–648. doi: 10.1136/adc.48.8.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee F. K., Nahmias A. J., Lowery S., Nesheim S., Reef S., Thompson S., Oleske J., Vahlne A., Czerkinsky C. ELISPOT: a new approach to studying the dynamics of virus-immune system interaction for diagnosis and monitoring of HIV infection. AIDS Res Hum Retroviruses. 1989 Oct;5(5):517–523. doi: 10.1089/aid.1989.5.517. [DOI] [PubMed] [Google Scholar]
- Lewis D. B., Yu C. C., Meyer J., English B. K., Kahn S. J., Wilson C. B. Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells. J Clin Invest. 1991 Jan;87(1):194–202. doi: 10.1172/JCI114970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mellander L., Carlsson B., Hanson L. A. Secretory IgA and IgM antibodies to E. coli O and poliovirus type I antigens occur in amniotic fluid, meconium and saliva from newborns. A neonatal immune response without antigenic exposure: a result of anti-idiotypic induction? Clin Exp Immunol. 1986 Mar;63(3):555–561. [PMC free article] [PubMed] [Google Scholar]
- Oldstone M. B., Tishon A., Moretta L. Active thymus derived suppressor lymphocytes in human cord blood. Nature. 1977 Sep 22;269(5626):333–335. doi: 10.1038/269333a0. [DOI] [PubMed] [Google Scholar]
- Pahwa S., Chirmule N., Leombruno C., Lim W., Harper R., Bhalla R., Pahwa R., Nelson R. P., Good R. A. In vitro synthesis of human immunodeficiency virus-specific antibodies in peripheral blood lymphocytes of infants. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7532–7536. doi: 10.1073/pnas.86.19.7532. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pahwa S., Pahwa R., Good R. A., Gallo R. C., Saxinger C. Stimulatory and inhibitory influences of human immunodeficiency virus on normal B lymphocytes. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9124–9128. doi: 10.1073/pnas.83.23.9124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palomba E., Gay V., Gabiano C., Perugini L., Tovo P. A. In-vitro production of HIV-1-specific antibody for diagnosis of perinatal infection. Lancet. 1990 Oct 13;336(8720):940–941. doi: 10.1016/0140-6736(90)92310-e. [DOI] [PubMed] [Google Scholar]
- Pyun K. H., Ochs H. D., Dufford M. T., Wedgwood R. J. Perinatal infection with human immunodeficiency virus. Specific antibody responses by the neonate. N Engl J Med. 1987 Sep 3;317(10):611–614. doi: 10.1056/NEJM198709033171006. [DOI] [PubMed] [Google Scholar]
- Quinn T. C., Kline R. L., Halsey N., Hutton N., Ruff A., Butz A., Boulos R., Modlin J. F. Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies. JAMA. 1991 Dec 25;266(24):3439–3442. [PubMed] [Google Scholar]
- SMITH R. T., EITZMAN D. V. THE DEVELOPMENT OF THE IMMUNE RESPONSE. CHARACTERIZATION OF THE RESPONSE OF THE HUMAN INFANT AND ADULT TO IMMUNIZATION WITH SALMONELLA VACCINES. Pediatrics. 1964 Feb;33:163–183. [PubMed] [Google Scholar]
- Splawski J. B., Lipsky P. E. Cytokine regulation of immunoglobulin secretion by neonatal lymphocytes. J Clin Invest. 1991 Sep;88(3):967–977. doi: 10.1172/JCI115400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Teeuwsen V. J., Lange J. M., Keet R., Schattenkerk J. K., Debouck C., van den Akker R., Goudsmit J., Osterhaus A. D. Low number of functionally active B lymphocytes in the peripheral blood of HIV-1-seropositive individuals with low p24-specific serum antibody titers. AIDS. 1991 Aug;5(8):971–979. doi: 10.1097/00002030-199108000-00008. [DOI] [PubMed] [Google Scholar]
- Tindall B., Cooper D. A. Primary HIV infection: host responses and intervention strategies. AIDS. 1991 Jan;5(1):1–14. [PubMed] [Google Scholar]
- Vendrell J. P., Segondy M., Ducos J., Reynes J., Huguet M. F., Nicolas J. C., Serre A. Analysis of the spontaneous in vitro anti-HIV-1 antibody secretion by peripheral blood mononuclear cells in HIV-1 infection. Clin Exp Immunol. 1991 Feb;83(2):197–202. doi: 10.1111/j.1365-2249.1991.tb05614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhou E. M., Chanh T. C., Dreesman G. R., Kanda P., Kennedy R. C. Immune response to human immunodeficiency virus. In vivo administration of anti-idiotype induces an anti-gp160 response specific for a synthetic peptide. J Immunol. 1987 Nov 1;139(9):2950–2956. [PubMed] [Google Scholar]