title: Potent autologous and heterologous neutralizing antibody responses occur in HIV-2 infection across a broad range of infection outcomes.
abstract: Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC(50)], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC(50)s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection.
authors.affiliation: Medical Research Council (United Kingdom) Laboratories, Fajara, the Gambia. thushandesilva@hotmail.com
authors.forename: Thushan I
authors.initials: TI
authors.lastname: de Silva
authors.forename: Marlén
authors.initials: M
authors.lastname: Aasa-Chapman
authors.forename: Matthew
authors.initials: M
authors.lastname: Cotten
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hué
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
authors.forename: Ramu
authors.initials: R
authors.lastname: Sarge-Njie
authors.forename: Neil
authors.initials: N
authors.lastname: Berry
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Robin
authors.initials: R
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000917:Antibody Formation; D002460:Cell Line; D015331:Cohort Studies; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D015498:HIV-2 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus
references.citation: Bioinformatics. 2005 May 15;21(10):2531-3
references.pmid: 15713735
references.citation: Hum Vaccin. 2011 Apr;7(4):466-73
references.pmid: 21389779
references.citation: J Virol. 2007 May;81(10):5331-8
references.pmid: 17301136
references.citation: J Virol. 2005 Mar;79(5):2823-30
references.pmid: 15709001
references.citation: Annu Rev Immunol. 1997;15:271-96
references.pmid: 9143689
references.citation: J Virol Methods. 2010 Sep;168(1-2):114-20
references.pmid: 20451557
references.citation: J Infect Dis. 2010 Oct 15;202 Suppl 2:S315-22
references.pmid: 20846039
references.citation: Virology. 2005 Sep 1;339(2):226-38
references.pmid: 16005039
references.citation: J Hum Virol. 1998 Nov-Dec;1(7):457-68
references.pmid: 10195267
references.citation: J Clin Invest. 2007 Oct;117(10):3067-74
references.pmid: 17823657
references.citation: AIDS Res Hum Retroviruses. 2002 Nov 1;18(16):1167-73
references.pmid: 12487822
references.citation: Bioinformatics. 2007 Nov 1;23(21):2947-8
references.pmid: 17846036
references.citation: Expert Rev Anti Infect Ther. 2011 Feb;9(2):195-206
references.pmid: 21342067
references.citation: J Gen Virol. 2005 Dec;86(Pt 12):3385-3396
references.pmid: 16298986
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9
references.pmid: 12644702
references.citation: PLoS Pathog. 2009 Sep;5(9):e1000598
references.pmid: 19763271
references.citation: J Virol. 2004 May;78(10):5205-15
references.pmid: 15113902
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18514-9
references.pmid: 16339909
references.citation: J Virol. 2007 Feb;81(3):1350-9
references.pmid: 17079307
references.citation: J Virol. 2005 Jul;79(14):8979-90
references.pmid: 15994792
references.citation: Virology. 2006 Sep 15;353(1):144-54
references.pmid: 16814357
references.citation: Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
references.pmid: 12019106
references.citation: PLoS Comput Biol. 2010 Aug 19;6(8):
references.pmid: 20808876
references.citation: J Virol. 2006 May;80(10):4758-70
references.pmid: 16641269
references.citation: Biochem Biophys Res Commun. 1999 May 10;258(2):313-21
references.pmid: 10329384
references.citation: J Virol. 2005 Sep;79(18):11848-57
references.pmid: 16140761
references.citation: Infect Genet Evol. 2005 Apr;5(3):239-46
references.pmid: 15737915
references.citation: Eur J Immunol. 2010 Jul;40(7):1963-72
references.pmid: 20411566
references.citation: J Infect Dis. 1999 Oct;180(4):1116-21
references.pmid: 10479138
references.citation: J Virol. 2009 Jan;83(2):662-72
references.pmid: 18987151
references.citation: Curr HIV Res. 2007 Nov;5(6):578-87
references.pmid: 18045114
references.citation: J Virol. 2008 Apr;82(8):3952-70
references.pmid: 18256145
references.citation: J Virol. 1994 Nov;68(11):7433-47
references.pmid: 7933127
references.citation: Nucleic Acids Res. 1990 Apr 11;18(7):1687-91
references.pmid: 2186361
references.citation: Curr Opin HIV AIDS. 2009 Sep;4(5):358-63
references.pmid: 20048698
references.citation: Mol Biol Evol. 2005 May;22(5):1208-22
references.pmid: 15703242
references.citation: Virology. 2006 Aug 1;351(2):489-96
references.pmid: 16712896
references.citation: Microbes Infect. 2008 Apr;10(5):455-61
references.pmid: 18407775
references.citation: Glycobiology. 2004 Dec;14(12):1229-46
references.pmid: 15175256
references.citation: J Virol. 2010 Feb;84(3):1439-52
references.pmid: 19939925
references.citation: Mol Biol Evol. 2006 Oct;23(10):1891-901
references.pmid: 16818476
references.citation: J Virol. 2009 Oct;83(19):10269-74
references.pmid: 19640996
references.citation: Virology. 2010 Dec 20;408(2):174-82
references.pmid: 20947116
references.citation: J Virol. 2000 Feb;74(3):1554-7
references.pmid: 10627569
references.citation: J Virol. 2001 Nov;75(21):10200-7
references.pmid: 11581388
references.citation: Vaccine. 2010 May 26;28 Suppl 2:B60-7
references.pmid: 20510746
references.citation: Retrovirology. 2007 Sep 24;4:67
references.pmid: 17892568
references.citation: J Virol. 2009 Feb;83(3):1240-59
references.pmid: 19019969
references.citation: J Exp Med. 2005 May 2;201(9):1407-19
references.pmid: 15867093
references.citation: J Infect Dis. 1996 Jan;173(1):245-8
references.pmid: 8537668
references.citation: J Virol. 2008 Aug;82(16):7932-41
references.pmid: 18524815
references.citation: J Virol. 2006 Nov;80(21):10884-9
references.pmid: 17041228
references.citation: AIDS. 2008 Jun 19;22(10):1195-202
references.pmid: 18525265
references.citation: PLoS One. 2011 Jan 20;6(1):e14548
references.pmid: 21283793
references.citation: J Immunol. 2006 Jun 1;176(11):6973-81
references.pmid: 16709858
references.citation: Nature. 2003 Mar 20;422(6929):307-12
references.pmid: 12646921
references.citation: PLoS One. 2009;4(2):e4505
references.pmid: 19229336
references.citation: J Virol. 2009 Nov;83(22):11966-78
references.pmid: 19740980
references.citation: PLoS Pathog. 2009 Sep;5(9):e1000594
references.pmid: 19763269
references.citation: J Acquir Immune Defic Syndr. 2010 Apr;53(5):640-7
references.pmid: 19841588
references.citation: Virology. 1993 Mar;193(1):528-30
references.pmid: 8438591
references.citation: J Virol. 2010 Dec;84(23):12429-36
references.pmid: 20844029
references.citation: J Virol. 2010 Apr;84(7):3516-27
references.pmid: 20089656
references.citation: Trends Microbiol. 2008 Dec;16(12):588-95
references.pmid: 18964021
references.citation: J Virol. 1994 Nov;68(11):7467-81
references.pmid: 7933130
references.citation: J Virol. 2006 Jan;80(2):835-44
references.pmid: 16378985
references.citation: J Virol. 1992 Jun;66(6):3531-7
references.pmid: 1583722
references.citation: PLoS One. 2011;6(8):e23961
references.pmid: 21887353
references.citation: Retrovirology. 2010 May 19;7:46
references.pmid: 20482865
references.citation: PLoS Comput Biol. 2006 Jun 23;2(6):e62
references.pmid: 16789820
references.citation: AIDS. 2003 Feb 14;17(3):291-300
references.pmid: 12556682
references.citation: J Virol. 2007 Jun;81(12):6187-96
references.pmid: 17409164
references.citation: J Infect Dis. 2007 Mar 1;195(5):726-33
references.pmid: 17262716
references.citation: J Virol. 2006 Jun;80(12):6155-64
references.pmid: 16731954
references.citation: J Virol. 2012 Jan;86(2):947-60
references.pmid: 22031948
references.citation: Nature. 1987 Apr 16-22;326(6114):662-9
references.pmid: 3031510
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W700-3
references.pmid: 16845102
references.citation: Infect Genet Evol. 2010 Apr;10(3):380-5
references.pmid: 19822224
references.citation: J Virol. 2006 Oct;80(19):9586-98
references.pmid: 16973562
references.citation: J Virol. 2000 Oct;74(20):9594-600
references.pmid: 11000231