Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160
Tóm tắt
Serum antibody responses were studied in detail in four vaccinia-naive volunteers in a phase I trial evaluating primary vaccination with a recombinant vaccinia virus expressing the HIV-1 gp160 envelope glycoprotein (HIVAC-1e, Oncogen/Bristol-Myers Squibb), followed by booster immunization with baculovirus-derived rgp160 (VaxSyn, MicroGeneSys). Prior to boosting, low-titer Fc receptor (FcR)-mediated, antibody-dependent enhancing (ADE) activity was detected in two of four volunteers but no IgM, IgG, IgA, neutralizing activity, or complement-mediated ADE activity was detected. Two weeks after boosting, all four volunteers developed HIV-1-specific IgG with titers of 1:160 to 1:640 by immunofluorescence assay. IgG1 was present in sera from each individual, while IgG2 and IgG3 were present in sera from two individuals, and IgG4 was present in serum from one individual. IgM and IgA were undetectable in all sera. Only one volunteer had IgG to the heterologous HIV-1 isolates, RF, MN, and SF2, after boosting. Serum from this volunteer neutralized the vaccine strain, LAV/IIIB, but not the heterologous strains, RF, MN, and SF2. Antibodies from the remaining volunteers had no neutralizing activity. The neutralizing serum had a positive reaction in a peptide-based ELISA utilizing a peptide corresponding to the principal neutralizing domain of the third hypervariable region (i.e., V3 loop) of the envelope glycoprotein. Neutralizing activity was partially removed by adsorption to this peptide, suggesting that it contained a type-specific neutralizing vaccine epitope. A low titer (1:40 to 1:80) of complement-mediated ADE activity to HIV-1 IIIB was present in sera from three vaccinees after boosting. FcR-ADE activity for HIV-1 SF2 and SF-128A were present in sera from two of these three vaccinees. None of the volunteers developed antisyncytial antibodies. These results indicate that inoculation with recombinant vaccinia followed by rgp160 boosting is the most effective strategy to date for inducing serum antibodies to the envelope glycoproteins of HIV-1, but further study is needed to optimize the functionality and cross-reactivity of these responses.
Tài liệu tham khảo
Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM: High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med 324:954, 1991
Daar ES, Moudgil T, Meyer RD, Ho DD: Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 324:961, 1991
Goudsmit J, Paul DA, Lange JMA, Speelman H, Van Der Noordaa J, Van Der Helm HJ, deWolf F, Epstein LG, Krone WJA, Wolters EC, Oleske JM, Coutinho RA: Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet 2:177, 1986
Stramer SL, Heller JS, Coombs RW, Parry JV, Ho DD, Allain J-P: Markers of HIV infection prior to IgG antibody seropositivity. JAMA 262:64, 1989
Albert J, Abrahamsson B, Nagy K, Aurelius E, Gaines H, Nystrom G, Fenyo EM: Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS 4:107–112, 1990
Tremblay M, Wainberg MA: Neutralization of multiple HIV-1 isolates from a single subject by autologous sequential sera. J Infect Dis 162:735–737, 1990
Nara PL, Smit L, Dunlop N, Hatch W, Merges M, Waters D, Kelliher J, Gallo RC, Fischinger PJ, Goudsmit J: Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol 64:3779–3791, 1990
Karpas A, Hill F, Youle M, Cullen V, Gray J, Byron N, Hayhoe F, Tenant-Flowers M, Howard L, Gilgen D, Oates JK, Hawkens D, Gazzard B: Effects of passive immunization in patients with the acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome. Proc Natl Acad Sci USA 85:9234, 1988
Karpas A, Hewlett IK, Hill F, Gray J, Byron N, Gilgen D, Bally V, Oates JK, Gazzard B, Epstein JE: Polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with AIDS and AIDS-related complex. Proc Natl Acad Sci USA 87:7613, 1990
Emini EA, Schleif WA, Nunberg JH, Conley AJ, Eda T, Tokiyoshi S, Putney SD, Matsushita S, Cobb KE, Jett CM, Eichberg JW, Murthy KK: Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature 355:728–730, 1992
Prince AM, Horowitz B, Shulman RW, Pascual D, Hewlett I, Epstein J, Eichberg JW: Apparent protection of HIV infection by HIV immunoglobulin given prior to low-dose HIV challenge.In Vaccines 90, F Brown, RM Chanock, HS Ginsberg, RA Lerner, (eds). Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, pp 347–351
Prince AM, Reesink H, Pascual D, Horowitz B, Hewlett I, Murthy KK, Cobb KE, Eichberg JW: Prevention of HIV infection by passive immunization with HIV immunoglobulin. AIDS Res Hum Retrovir 7:971–973, 1991
Girard M, Kieny M-P, Pinter A, Barre-Sinoussi F, Nara P, Kolbe H, Kusumi K, Chaput A, Reinhart T, Muchmore E, Ronco J, Kaczorek M, Gomard E, Gluckman J-C, Fultz PN: Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci USA 88:542–546, 1991
Berman PW, Gregory TJ, Riddle L, Nakamura GR, Champe MA, Porter JP, Wurm FM, Hershberg RD, Cobb EK, Eichberg JW: Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature 345:622–625, 1990
Robinson WE, Montefiori DC, Mitchell WM: Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet 1:790, 1988
Takeda A, Tuazon CU, Ennis FA: Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science 242:580, 1988
Homsy J, Meyer M, Levy JA: Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. J Virol 64:1437, 1990
Montefiori DC, Lefkowitz LB, Keller RE, Holmberg V, Sandstrom E, Phair JP, Multicenter AIDS Cohort Study Group: Absence of a clinical correlation for complement-mediated, infection-enhancing antibodies in plasma and sera from HIV-1 infected persons. AIDS 5:513, 1991
Toth FD, Szabo B, Ujhelyi E, Paloczi K, Horvath A, Fust G, Kiss J, Banhegyi D, Hollan SR: Neutralizing and complement-dependent enhancing antibodies in different stages of HIV infection. AIDS 5:263, 1991
Dolin R, Graham BS, Greenberg SB, Tacket CO, Belshe RB, Midthun K, Clements ML, Gorse GJ, Horgan BW, Atmar RL, Karzon DT, Bonnez W, Fernie BF, Montefiori DC, Stablien DM, Smith GE, Koff WC, NIAID AIDS Vaccine Clinical Trials Network: The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. Ann Intern Med 114:119, 1991
Archibald DW, Hebert CA, Sun D, Tacket CO: Salivary antibodies to human immunodeficiency virus type 1 in a phase I AIDS vaccine trial. J Acquir Immu Defic Syndr 3:954, 1990
Keefer MC, Bonnez W, Roberts NJ, Dolin R, Reichman RC: Human immunodeficiency virus (HIV-1) gp160-specific lymphocyte proliferation responses of mononuclear leukocytes from HIV-1 recombinant gp160 vaccine recipients. J Infect Dis 163:448, 1991
Tacket CO, Baqar S, Munoz C, Murphy JR: Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160. AIDS Res Hum Retrovir 6:535, 1990
Orentas RJ, Hildreth JEK, Obah E, Polydefkis M, Smith GE, Clemens ML, Siliciano RF: Induction of CD4+ human cytolytic T cells specific for HIV-infected cells by a gp160 subunit vaccine. Science 248:1234, 1990
Graham BS, Matthews TJ, Belshe RB, Clements ML, Dolin R, Wright PW, Gorse GJ, Schwartz DH, Keefer MC, Bolognesi DP, Corey L, Stablein DM, Esterlitz JR, Hu S-L, Smith GE, Fast PE, Koff WC, NIAID AIDS Vaccine Clinical Trials Network: Augmentation of HIV-1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160. J Infect Dis (in press)
Cooney EL, Coombs RW, Hoffman MC, Collier AC, Zarling J, Hu S-L, Greenberg PD, Arditti DE, Corey L: Safety and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet 337:567–572, 1991
Graham BS, Belshe RB, Clements ML, Dolin R, Corey L, Wright PF, Gorse GJ, Midthun K, Keefer MC, Roberts NJ, Schwartz DH, Agosti JM, Fernie BF, Stablein DM, Montefiori DC, Lambert JS, Hu S-L, Esterlitz JR, Lawrence DN, Koff WC, AIDS Vaccine Clinical Trials Network: Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. J Infect Dis 166:244, 1992
Hu S-L, Kosowski SG, Dalrymple JM: Expression of AIDS virus envelope gene in recombinant vaccinia viruses. Nature 320:537, 1986
Cochran MA, Ericson BL, Knell JD: Use of baculovirus recombinants as a general method for the production of subunit vaccines.In Vaccines 87. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1987, p 384
Wain-Hobson S, Vartanian J-P, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre M-T, Guetard D, Klazmann D, Gluckman J-C, Rozenbaum W, Barre-Sinnoussi F, Montagnier L: LAV revisited: Origins of the early HIV-1 isolates from Institut Pasteur. Science 252:961, 1991
Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nagata K, Hinuma Y: Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature 294:770, 1991
Cheng-Mayer C, Homsy J, Evans LA, Levy JA: Identification of human immunodeficiency virus subtypes with distinct patterns of sensitivity to serum neutralization. Proc Natl Acad Sci USA 85:2815–2819, 1988
Castro BA, Weiss CD, Wiviot LD, Levy JA: Optimal conditions for recovery of human immunodeficiency virus from peripheral blood mononuclear cells. J Clin Microbiol 26:2371–2376, 1988
Hoffman AD, Banapour B, Levy JA: Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for detection in virions. Virol 147:326–335, 1985
McDougal JS, Cort SP, Kennedy MS, Cabridilla CD, Feorino PM, Francis DP, Hicks D, Kalyanaraman VS, Martin JS: Immunoassay for the detection and quantitation of infectious human retrovirus, lymphadenopathy-associated virus (LAV). J Immunol Methods 76:171–183, 1985
Javaherian K, Langlois AJ, McDanal C, Ross KL, Eckler LI, Jellis CJ, Profy AT, Ruschie JR, Bolognesi DP, Putney SD, Matthews TJ: Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci USA 86:6768, 1989
Montefiori DC, Robinson WE, Schuffman SS, Mitchell: Evaluation of antiviral drugs and neutralizing antibodies against human immunodeficiency virus by a rapid and sensitive microtiter infection assay. J Clin Microbiol 26:231, 1988
Graham BS, Rowland JM, Modliszewski A, Montefiori DC: Anti-fusion activity in sera from HIV-1 infected persons. J Clin Microbiol 28:2608, 1990
Hu S-L, Klaniecki J, Dykers T, Sridhar P, Travis BM: Neutralizing antibodies against HIV-1 BRU and SF2 isolates generated in mice immunized with recombinant vaccinia virus expressing HIV-1 (BRU) envelope glycoproteins and boosted with homologous gp160. AIDS Res Hum Retrovir 7:615, 1991
Hu S-L, Abrams K, Barber GN, Moran P, Zarling JM, Langlois AJ, Kuller L, Morton WR, Benveniste RE: Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science 255:456, 1992
Ljunggren K, Broliden P-A, Morfeldt-Manson L, Jondal M, Wahren B: IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages. Clin Exp Immunol 73:343, 1988
Khalife J, Guy B, Capron M, Kieny M-P, Ameisen J-C, Montagnier L, Lecocq J-P, Capron A: Isotypic restriction of antibody response to human immunodeficiency virus. AIDS Res Hum Retrovir 4:3, 1988
Chiodi F, Mathiesen T, Albert J, Parks E, Norrby E, Wahren B: IgG subclass responses to a transmembrane protein (gp41) peptide in HIV infection. J Immunol 142:3809, 1989
Viscidi R, Ellerbeck E, Garrison L, Midthun K, Clemens ML, Clayman B, Fernie B, Smith G, NIAID AIDS Vaccine Clinical Trials Network: Characterization of serum antibody responses to recombinant HIV-1 gp160 vaccine by enzyme immunoassay. AIDS Res Hum Retrovir 6:1251, 1990
Palker TJ, Clark ML, Langlois AJ, Matthews TJ, Weinhold KJ, Randall R, Bolognesi, DP, Haynes BF: Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci USA 85:1932, 1988
Steimer KS, Scandella CJ, Skiles PV, Haigwood NL: Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to gp120. Science 254:105, 1991
Tilley SA, Honnen WJ, Racho M, Hilgartner M, Pinter A: A human monoclonal antibody against the CD4 binding site of HIV-1 gp120 exhibits potent, broadly neutralizing activity. Res Virol 142:247, 1991
Ho DD, McKeating JA, Li XL, Moudgil T, Daar ES, Sun N, Robinson JE: Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody. J Virol 65:489, 1991
Posner MR, Hideshima T, Cannon T, Mukherjee M, Mayer KH, Byrn RA: An IgG human monoclonal antibody that reacts with HIV-1/gp120, inhibits virus binding to cells, and neutralizes infection. J Immunol 146:4325, 1991
Dalgleish AG, Chanh TC, Kennedy RC, Kanda P, Clapham PR, Weiss RA: Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide. Virol 165:209, 1988
Halsteadt SB: Immune enhancement of viral infection. Prog Allergy 31:301, 1982
Robinson WE, Gorny MK, Xu J-Y, Mitchell WM, Zolla-Pazner S: Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro. J Virol 65:4169–4176, 1991
Kliks S, Wu WW, Levy JA: V3 epitopes can mediate antibody neutralization and enhancement of HIV-1 infection. VII International Conference on AIDS, 1991, abstr
D'Souza MP, Durda P, Hanson CV, Milman G: Evaluation of monoclonal antibodies to HIV-1 by neutralization and serological assays: An international collaboration. AIDS 5:1061–1070, 1991