| Title: |
Envelope-Specific Recognition Patterns of HIV Vaccine-Induced IgG Antibodies Are Linked to Immunogen Structure and Sequence |
| Authors: |
Nadai, Y; Held, K; Joseph, S; Ahmed, MIM; Hoffmann, VS; Peterhoff, D; Missange, M; Bauer, A; Joachim, A; Reimer, U; Zerweck, J; McCormack, S; Cope, A; Tatoud, R; Shattock, RJ; Robb, ML; Sandstroem, EG; Hoelscher, M; Maboko, L; Bakari, M; Kroidl, A; Wagner, R; Weber, J; Pollakis, G; Geldmacher, C |
| Source: |
Frontiers in Immunology , 10 , Article 717. (2019) |
| Publisher Information: |
FRONTIERS MEDIA SA |
| Publication Year: |
2019 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
HIV; vaccine; envelope-specific antibodies; epitope variant recognition; immunogen structure; immunogen sequence |
| Description: |
BACKGROUND: A better understanding of the parameters influencing vaccine-induced IgG recognition of individual antigenic regions and their variants within the HIV Envelope protein (Env) can help to improve design of preventive HIV vaccines. METHODS: Env-specific IgG responses were mapped in samples of the UKHVC003 Standard Group (UK003SG, n = 11 from UK) and TaMoVac01 (TMV01, n = 17 from Tanzania) HIV vaccine trials. Both trials consisted of three immunizations with DNA, followed by two boosts with recombinant Modified Vaccinia Virus Ankara (MVA), either mediating secretion of gp120 (UK003SG) or the presentation of cell membrane bound gp150 envelopes (TMV01) from infected cells, and an additional two boosts with 5 μg of CN54gp140 protein adjuvanted with glucopyranosyl lipid adjuvant (GLA). Env immunogen sequences in UK003SG were solely based on the clade C isolate CN54, whereas in TMV01 these were based on clades A, C, B, and CRF01AE. The peptide microarray included 8 globally representative Env sequences, CN54gp140 and the MVA-encoded Env immunogens from both trials, as well as additional peptide variants for hot spots of immune recognition. RESULTS: After the second MVA boost, UK003SG vaccinees almost exclusively targeted linear, non-glycosylated antigenic regions located in the inter-gp120 interface. In contrast, TMV01 recipients most strongly targeted the V2 region and an immunodominant region in gp41. The V3 region was frequently targeted in both trials, with a higher recognition magnitude for diverse antigenic variants observed in the UK003SG (p < 0.0001). After boosting with CN54gp140/GLA, the overall response magnitude increased with a more comparable recognition pattern of antigenic regions and variants between the two trials. Recognition of most immunodominant regions within gp120 remained significantly stronger in UK003SG, whereas V2-region recognition was not boosted in either group. CONCLUSIONS: IgG recognition of linear antigenic Env regions differed between the two trials particularly after the ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10074477/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10074477/7/McCormack_Envelope-Specific%20Recognition%20Patterns%20of%20HIV%20Vaccine-Induced%20IgG%20Antibodies%20Are%20Linked%20to%20Immunogen%20Structure%20and%20Sequence_VoR.pdf; https://discovery.ucl.ac.uk/id/eprint/10074477/ |
| Rights: |
open |
| Accession Number: |
edsbas.B5B35754 |
| Database: |
BASE |