PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
 
J Virol. 1997 July; 71(7): 5069–5079.
PMCID: PMC191740

Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity.

Abstract

Previous studies of attenuated simian immunodeficiency virus (SIV) vaccines in rhesus macaques have demonstrated the development of broad protection against experimental challenge, indicating the potential for the production of highly effective immune responses to SIV antigens. However, the development of this protective immune status was found to be critically dependent on the length of time postvaccination with the attenuated virus strain, suggesting a necessary maturation of immune responses. In this study, the evolution of SIV envelope-specific antibodies in monkeys experimentally infected with various attenuated strains of SIV was characterized by using a comprehensive panel of serological assays to assess the progression of antibodies in longitudinal serum samples that indicate the development of protective immunity. In parallel studies, we also used the same panel of antibody assays to characterize the properties of SIV envelope-specific antibodies elicited by inactivated whole-virus and envelope subunit vaccines previously reported to be ineffective in producing protective immunity. The results of these studies demonstrate that the evolution of protective immunity in monkeys inoculated with attenuated strains of SIV is associated with a complex and lengthy maturation of antibody responses over the first 6 to 8 months postinoculation, as reflected in progressive changes in antibody conformational dependence and avidity properties. The establishment of long-term protective immunity at this time in general parallels the absence of further detectable changes in antibody responses and a maintenance of relatively constant antibody titer, avidity, conformational dependence, and the presence of neutralizing antibody for at least 2 years postinoculation. In contrast to the mature antibody responses elicited by the attenuated SIV vaccines, the whole-virus and envelope subunit vaccines in general elicited only immature antibody responses characterized by poor reactivity with native envelope proteins, low avidity, low conformational dependence, and the absence of neutralization activity against the challenge strain. Thus, these studies establish for the first time an association between the effectiveness of experimental vaccines and the capacity of the vaccine to produce a mature antibody response to SIV envelope proteins and further indicate that a combination of several antibody parameters (including titer, avidity, conformational dependence, and virus neutralization) are superior to any single antibody parameter as prognostic indicators to evaluate candidate AIDS vaccines.

Full Text

The Full Text of this article is available as a PDF (171K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anderson MG, Hauer D, Sharma DP, Joag SV, Narayan O, Zink MC, Clements JE. Analysis of envelope changes acquired by SIVmac239 during neuroadaption in rhesus macaques. Virology. 1993 Aug;195(2):616–626. [PubMed]
  • Andersson A, Vetter V, Kreutzer L, Bauer G. Avidities of IgG directed against viral capsid antigen or early antigen: useful markers for significant Epstein-Barr virus serology. J Med Virol. 1994 Jul;43(3):238–244. [PubMed]
  • Baskin GB, Martin LN, Rangan SR, Gormus BJ, Murphey-Corb M, Wolf RH, Soike KF. Transmissible lymphoma and simian acquired immunodeficiency syndrome in rhesus monkeys. J Natl Cancer Inst. 1986 Jul;77(1):127–139. [PubMed]
  • Blackburn NK, Besselaar TG, Schoub BD, O'Connell KF. Differentiation of primary cytomegalovirus infection from reactivation using the urea denaturation test for measuring antibody avidity. J Med Virol. 1991 Jan;33(1):6–9. [PubMed]
  • Boppana SB, Britt WJ. Antiviral antibody responses and intrauterine transmission after primary maternal cytomegalovirus infection. J Infect Dis. 1995 May;171(5):1115–1121. [PubMed]
  • Broström C, Sönnerberg A, Sällberg M. Human immunodeficiency virus type 1-infected patients with no disease progression display high-avidity antibody production to autologous V3 sequences. J Infect Dis. 1995 Feb;171(2):509–511. [PubMed]
  • Chargelegue D, O'Toole CM, Colvin BT. A longitudinal study of the IgG antibody response to HIV-1 p17 gag protein in HIV-1+ patients with haemophilia: titre and avidity. Clin Exp Immunol. 1993 Sep;93(3):331–336. [PubMed]
  • Chargelegue D, Stanley CM, O'Toole CM, Colvin BT, Steward MW. The absence of loss of antibodies of high affinity to human immunodeficiency virus (HIV) is associated with disease progression in HIV-1-infected patients. J Infect Dis. 1995 Sep;172(3):897–898. [PubMed]
  • Clements JE, Montelaro RC, Zink MC, Amedee AM, Miller S, Trichel AM, Jagerski B, Hauer D, Martin LN, Bohm RP, et al. Cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus. J Virol. 1995 May;69(5):2737–2744. [PMC free article] [PubMed]
  • Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science. 1992 Dec 18;258(5090):1938–1941. [PubMed]
  • Desrosiers RC. The simian immunodeficiency viruses. Annu Rev Immunol. 1990;8:557–578. [PubMed]
  • Devash Y, Calvelli TA, Wood DG, Reagan KJ, Rubinstein A. Vertical transmission of human immunodeficiency virus is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal neutralizing domain. Proc Natl Acad Sci U S A. 1990 May;87(9):3445–3449. [PubMed]
  • Gray JJ. Avidity of EBV VCA-specific IgG antibodies: distinction between recent primary infection, past infection and reactivation. J Virol Methods. 1995 Mar;52(1-2):95–104. [PubMed]
  • Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC. Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. J Virol. 1997 May;71(5):3840–3852. [PMC free article] [PubMed]
  • Hedman K, Hietala J, Tiilikainen A, Hartikainen-Sorri AL, Räihä K, Suni J, Vänänen P, Pietiläinen M. Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing. J Med Virol. 1989 Apr;27(4):293–298. [PubMed]
  • Hedman K, Seppälä I. Recent rubella virus infection indicated by a low avidity of specific IgG. J Clin Immunol. 1988 May;8(3):214–221. [PubMed]
  • Junker AK, Tilley P. Varicella-zoster virus antibody avidity and IgG-subclass patterns in children with recurrent chickenpox. J Med Virol. 1994 Jun;43(2):119–124. [PubMed]
  • Kangro HO, Manzoor S, Harper DR. Antibody avidity following varicella-zoster virus infections. J Med Virol. 1991 Feb;33(2):100–105. [PubMed]
  • Langlois AJ, Weinhold KJ, Matthews TJ, Greenberg ML, Bolognesi DP. The ability of certain SIV vaccines to provoke reactions against normal cells. Science. 1992 Jan 17;255(5042):292–293. [PubMed]
  • Lewis MG, Elkins WR, McCutchan FE, Benveniste RE, Lai CY, Montefiori DC, Burke DS, Eddy GA, Shafferman A. Passively transferred antibodies directed against conserved regions of SIV envelope protect macaques from SIV infection. Vaccine. 1993 Oct;11(13):1347–1355. [PubMed]
  • Lohman BL, McChesney MB, Miller CJ, McGowan E, Joye SM, Van Rompay KK, Reay E, Antipa L, Pedersen NC, Marthas ML. A partially attenuated simian immunodeficiency virus induces host immunity that correlates with resistance to pathogenic virus challenge. J Virol. 1994 Nov;68(11):7021–7029. [PMC free article] [PubMed]
  • Lu S, Arthos J, Montefiori DC, Yasutomi Y, Manson K, Mustafa F, Johnson E, Santoro JC, Wissink J, Mullins JI, et al. Simian immunodeficiency virus DNA vaccine trial in macaques. J Virol. 1996 Jun;70(6):3978–3991. [PMC free article] [PubMed]
  • Meurman O, Waris M, Hedman K. Immunoglobulin G antibody avidity in patients with respiratory syncytial virus infection. J Clin Microbiol. 1992 Jun;30(6):1479–1484. [PMC free article] [PubMed]
  • Montefiori DC, Reimann KA, Letvin NL, Zhou J, Hu SL. Studies of complement-activating antibodies in the SIV/macaque model of acute primary infection and vaccine protection. AIDS Res Hum Retroviruses. 1995 Aug;11(8):963–970. [PubMed]
  • Montelaro RC, Grund C, Raabe M, Woodson B, Cook RF, Cook S, Issel CJ. Characterization of protective and enhancing immune responses to equine infectious anemia virus resulting from experimental vaccines. AIDS Res Hum Retroviruses. 1996 Mar 20;12(5):413–415. [PubMed]
  • Morgan-Capner P, Thomas HI. Serological distinction between primary rubella and reinfection. Lancet. 1988 Jun 18;1(8599):1397–1397. [PubMed]
  • Murphey-Corb M, Martin LN, Davison-Fairburn B, Montelaro RC, Miller M, West M, Ohkawa S, Baskin GB, Zhang JY, Putney SD, et al. A formalin-inactivated whole SIV vaccine confers protection in macaques. Science. 1989 Dec 8;246(4935):1293–1297. [PubMed]
  • Murphey-Corb M, Montelaro RC, Miller MA, West M, Martin LN, Davison-Fairburn B, Ohkawa S, Baskin GB, Zhang JY, Miller GB, et al. Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys. AIDS. 1991 Jun;5(6):655–662. [PubMed]
  • Ohkawa S, Xu K, Wilson LA, Montelaro R, Martin LN, Murphey-Corb M. Analysis of envelope glycoprotein-specific antibodies from SIV-infected and gp110-immunized monkeys in ACC and ADCC assays. AIDS Res Hum Retroviruses. 1995 Mar;11(3):395–403. [PubMed]
  • Polanec J, Seppälä I, Rousseau S, Hedman K. Evaluation of protein-denaturing immunoassays for avidity of immunoglobulin G to rubella virus. J Clin Lab Anal. 1994;8(1):16–21. [PubMed]
  • Regier DA, Desrosiers RC. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. [PubMed]
  • Robinson JE, Holton D, Liu J, McMurdo H, Murciano A, Gohd R. A novel enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to HIV-1 envelope glycoproteins based on immobilization of viral glycoproteins in microtiter wells coated with concanavalin A. J Immunol Methods. 1990 Aug 28;132(1):63–71. [PubMed]
  • Robinson JE, Holton D, Pacheco-Morell S, Liu J, McMurdo H. Identification of conserved and variant epitopes of human immunodeficiency virus type 1 (HIV-1) gp120 by human monoclonal antibodies produced by EBV-transformed cell lines. AIDS Res Hum Retroviruses. 1990 May;6(5):567–579. [PubMed]
  • Salmi AA. Antibody affinity and protection in virus infections. Curr Opin Immunol. 1991 Aug;3(4):503–506. [PubMed]
  • Sharma DP, Zink MC, Anderson M, Adams R, Clements JE, Joag SV, Narayan O. Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaques. J Virol. 1992 Jun;66(6):3550–3556. [PMC free article] [PubMed]
  • Simon F, Rahimy C, Krivine A, Levine M, Pepin JM, Lapierre D, Denamur E, Vernoux L, De Crepy A, Blot P, et al. Antibody avidity measurement and immune complex dissociation for serological diagnosis of vertically acquired HIV-1 infection. J Acquir Immune Defic Syndr. 1993 Feb;6(2):201–207. [PubMed]
  • Stott EJ. Anti-cell antibody in macaques. Nature. 1991 Oct 3;353(6343):393–393. [PubMed]
  • Thomas HI, Morgan-Capner P. Rubella-specific IgG1 avidity: a comparison of methods. J Virol Methods. 1991 Feb-Mar;31(2-3):219–228. [PubMed]
  • Thomas HI, Wilson S, O'Toole CM, Lister CM, Saeed AM, Watkins RP, Morgan-Capner P. Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1. Clin Exp Immunol. 1996 Feb;103(2):185–191. [PubMed]
  • Ward KN, Dhaliwal W, Ashworth KL, Clutterbuck EJ, Teo CG. Measurement of antibody avidity for hepatitis C virus distinguishes primary antibody responses from passively acquired antibody. J Med Virol. 1994 Aug;43(4):367–372. [PubMed]
  • Ward KN, Gray JJ, Joslin ME, Sheldon MJ. Avidity of IgG antibodies to human herpesvirus-6 distinguishes primary from recurrent infection in organ transplant recipients and excludes cross-reactivity with other herpesviruses. J Med Virol. 1993 Jan;39(1):44–49. [PubMed]
  • Wreghitt TG, Gray JJ, Aloyisus S, Contreras M, Barbara JA. Antibody avidity test for recent infection with hepatitis C virus. Lancet. 1990 Mar 31;335(8692):789–789. [PubMed]
  • Wyand MS, Manson KH, Garcia-Moll M, Montefiori D, Desrosiers RC. Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. J Virol. 1996 Jun;70(6):3724–3733. [PMC free article] [PubMed]
  • Zinkernagel RM. Immunology taught by viruses. Science. 1996 Jan 12;271(5246):173–178. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)