title: Complement-mediated virus infectivity neutralisation by HLA antibodies is associated with sterilising immunity to SIV challenge in the macaque model for HIV/AIDS.
abstract: Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed.
authors.affiliation: Division of Virology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Page
authors.affiliation: Division of Virology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts, United Kingdom.
authors.forename: Ruby
authors.initials: R
authors.lastname: Quartey-Papafio
authors.affiliation: Division of Virology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Robinson
authors.affiliation: Division of Virology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Hassall
authors.affiliation: Centre for Infection & Immunity, Division of Clinical Sciences, St George's, University of London, London, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Cranage
authors.affiliation: Division of Virology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Stott
authors.affiliation: Division of Virology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D006649:Histocompatibility Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*; D016896:Treatment Outcome; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D015164:Vaccines, Inactivated; D003165:Complement System Proteins