A Vaccine for HIV Type 1: the Antibody Perspective

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1997 Sep 18

PMID 9294155

Citations 63

Authors

D R Burton

Affiliations

Soon will be listed here.

Abstract

Antibodies that bind well to the envelope spikes of immunodeficiency viruses such as HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV) can offer protection or benefit if present at appropriate concentrations before viral exposure. The challenge in antibody-based HIV-1 vaccine design is to elicit such antibodies to the viruses involved in transmission in humans (primary viruses). At least two major obstacles exist. The first is that very little of the envelope spike surface of primary viruses appears accessible for antibody binding (low antigenicity), probably because of oligomerization of the constituent proteins and a high degree of glycosylation of one of the proteins. The second is that the mature oligomer constituting the spikes appears to stimulate only weak antibody responses (low immunogenicity). Viral variation is another possible obstacle that appears to present fewer problems than anticipated. Vaccine design should focus on presentation of an intact mature oligomer, increasing the immunogenicity of the oligomer and learning from the antibodies available that potently neutralize primary viruses.

Citing Articles

Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.

Joyce C, Murrell S, Murrell B, Omorodion O, Ver L, Carrico N PLoS Pathog. 2023; 19(6):e1011416.

PMID: 37384622 PMC: 10309625. DOI: 10.1371/journal.ppat.1011416.

Antiviral neutralizing antibodies: from in vitro to in vivo activity.

Burton D Nat Rev Immunol. 2023; 23(11):720-734.

PMID: 37069260 PMC: 10108814. DOI: 10.1038/s41577-023-00858-w.

Mining for humoral correlates of HIV control and latent reservoir size.

Das J, Devadhasan A, Linde C, Broge T, Sassic J, Mangano M PLoS Pathog. 2020; 16(10):e1008868.

PMID: 33048992 PMC: 7553335. DOI: 10.1371/journal.ppat.1008868.

Passive immunotherapy of viral infections: 'super-antibodies' enter the fray.

Walker L, Burton D Nat Rev Immunol. 2018; 18(5):297-308.

PMID: 29379211 PMC: 5918154. DOI: 10.1038/nri.2017.148.

HIV Vaccine Strategies - an Update.

Sahni A, Nagendra A Med J Armed Forces India. 2016; 60(2):157-64.

PMID: 27407611 PMC: 4923036. DOI: 10.1016/S0377-1237(04)80109-6.

References

Muster T, Steindl F, Purtscher M, Trkola A, Klima A, Himmler G . A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol. 1993; 67(11):6642-7. PMC: 238102. DOI: 10.1128/JVI.67.11.6642-6647.1993. View

Vittecoq D, Chevret S, Morand-Joubert L, Heshmati F, Audat F, Bary M . Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma. Proc Natl Acad Sci U S A. 1995; 92(4):1195-9. PMC: 42665. DOI: 10.1073/pnas.92.4.1195. View

Gardner M, Rosenthal A, Jennings M, Yee J, Antipa L, Robinson Jr E . Passive immunization of rhesus macaques against SIV infection and disease. AIDS Res Hum Retroviruses. 1995; 11(7):843-54. DOI: 10.1089/aid.1995.11.843. View

Sattentau Q, Moore J . Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer. J Exp Med. 1995; 182(1):185-96. PMC: 2192089. DOI: 10.1084/jem.182.1.185. View

Safrit J, Fung M, Andrews C, Braun D, Sun W, Chang T . hu-PBL-SCID mice can be protected from HIV-1 infection by passive transfer of monoclonal antibody to the principal neutralizing determinant of envelope gp120. AIDS. 1993; 7(1):15-21. DOI: 10.1097/00002030-199301000-00002. View

McCune J, Rabin L, Feinberg M, Lieberman M, KOSEK J, Reyes G . Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988; 53(1):55-67. DOI: 10.1016/0092-8674(88)90487-4. View

Weissenhorn W, Dessen A, Harrison S, Skehel J, Wiley D . Atomic structure of the ectodomain from HIV-1 gp41. Nature. 1997; 387(6631):426-30. DOI: 10.1038/387426a0. View

Barbas 3rd C, Bjorling E, Chiodi F, Dunlop N, Cababa D, Jones T . Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. Proc Natl Acad Sci U S A. 1992; 89(19):9339-43. PMC: 50122. DOI: 10.1073/pnas.89.19.9339. View

Sattentau Q, Zolla-Pazner S, Poignard P . Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. Virology. 1995; 206(1):713-7. DOI: 10.1016/s0042-6822(95)80094-8. View

10.

Levy J, Youvan T, Lee M . Passive hyperimmune plasma therapy in the treatment of acquired immunodeficiency syndrome: results of a 12-month multicenter double-blind controlled trial. The Passive Hyperimmune Therapy Study Group. Blood. 1994; 84(7):2130-5. View

11.

Trkola A, Dragic T, Arthos J, Binley J, Olson W, Allaway G . CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature. 1996; 384(6605):184-7. DOI: 10.1038/384184a0. View

12.

Putkonen P, Thorstensson R, Ghavamzadeh L, Albert J, Hild K, Biberfeld G . Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys. Nature. 1991; 352(6334):436-8. DOI: 10.1038/352436a0. View

13.

Burton D, Pyati J, Koduri R, Sharp S, Thornton G, Parren P . Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994; 266(5187):1024-7. DOI: 10.1126/science.7973652. View

14.

Moore J, Ho D . HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells. AIDS. 1995; 9 Suppl A:S117-36. View

15.

Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N . Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol. 1996; 70(2):1100-8. PMC: 189917. DOI: 10.1128/JVI.70.2.1100-1108.1996. View

16.

FRANCIS Jr T . Influenza: the new acquayantance. Ann Intern Med. 1953; 39(2):203-21. DOI: 10.7326/0003-4819-39-2-203. View

17.

Parren P, Gauduin M, Koup R, Poignard P, Fisicaro P, Burton D . Relevance of the antibody response against human immunodeficiency virus type 1 envelope to vaccine design. Immunol Lett. 1997; 57(1-3):105-12. DOI: 10.1016/s0165-2478(97)00043-6. View

18.

Deutsch S, Vinit M, BUSSARD A . Original antigenic sin at the cellular level. II. Specificity of the antibodies produced by individual cells. Eur J Immunol. 1973; 3(4):235-40. DOI: 10.1002/eji.1830030411. View

19.

Haigwood N, Watson A, Sutton W, McClure J, Lewis A, Ranchalis J . Passive immune globulin therapy in the SIV/macaque model: early intervention can alter disease profile. Immunol Lett. 1996; 51(1-2):107-14. DOI: 10.1016/0165-2478(96)02563-1. View

20.

Gelderblom H . Assembly and morphology of HIV: potential effect of structure on viral function. AIDS. 1991; 5(6):617-37. View