Detection of Vaccine Induced Mucosal Antibodies in Phase I HIV Preventative Vaccine Trials
Transcript of Detection of Vaccine Induced Mucosal Antibodies in Phase I HIV Preventative Vaccine Trials
BMI (‡ 30) correlated with 78% decreased odds of a positiveELISPOT response, p < 0.005 When analyzed as a continuousvariable, one unit increase in BMI correlated to a 8% decrease inthe odds of a positive ELISPOT response, p < 0.001. Daily orweekly alcohol use, compared to no alcohol use correlated with3-fold increase in the odds of positive ELISPOT responses(p < 0.05). Age, gender, and any drug use were not associatedwith ELISPOT responses.Conclusions: Overweight BMI appears to be associated withdecreased immune response to certain HIV vaccine candidateswhen measured by IFN-g ELISPOT in healthy, HIV low-riskpopulations. This effect may impact interpretation of phase Itrials which typically have small group sizes. The positive as-sociation with alcohol use deserves further analysis.
P26.04Detection of Vaccine Induced Mucosal Antibodiesin Phase I HIV Preventative Vaccine Trials
Phil Bergin1, Robert Langat2, Bashir Farah2, Simon Ogola2,Gloria Omosa-Manyonyi2, Gaudensia Mutua2, Gina Outtara2,Harriet Park3, Jennifer Lehrman3, Irene Mwangi2, HelenCoutinho1, Paramesh Chetty4, Martin McMorrow1, JosephineCox1, Pat Fast3, Dagna Laufer3, Jill Gilmour1, Omu Anzala2
1IAVI Human Immunology Laboratory, London, UnitedKingdom, 2Kenya AIDS Vaccine Initiative Institute of ClinicalResearch, Nairobi, Kenya, 3International AIDS Vaccine In-itiative, New York, NY, United States, 4International AIDSVaccine Initiative, Johannesburg, South Africa
Background: Mucosal HIV-specific antibodies may help toprevent acquisition of HIV-1. An efficacious vaccine may re-quire a mucosal immune response. We show that vaccine-induced antibodies can be found in mucosal fluids, albeit at lowfrequency.Methods: The Kenya AIDS Vaccine Initiative (KAVI) took partin 3 Ph1 HIV vaccine trials (B002, B003 and B004) at 2 sites inNairobi. Participants were consented for a mucosal sub-studyand asked to provide saliva (SA), oral fluid (OF), semen (SM),cervico-vaginal (CV) and rectal (RC) specimens. Specimenswere collected at baseline and 2 post-vaccination time points andIgG and IgA against either HIV-1 Gag (p24; B002 and B004) orEnv (gp140; B003 and B004) were measured by ELISA, sam-ples giving a positive reading (by absorbance) were then titrated.IgA and IgG antibodies in serum or plasma (SPL) were alsomeasured at the same time points. Concordance was confirmedbetween assays at KAVI and the IAVI Human ImmunologyLaboratory, London.Results: Of 105 Kenyan participants, 89 consented to the sub-study and provided at least one mucosal sample type. Anti-HIVIgG and/or IgA antibodies tested, to date, were detected in 32/193 (17%) oral fluid/parotid saliva, 13/42 (31%) SM, 12/82(15%) CV, 8/27 (30%) RC and 68/84 (81%) of SPL samples. InSA, OF, CV and SM samples most antibody responses were IgG,while there were more volunteers with IgA in the RC samples.Some RC samples had low levels of IgA antibody reactivityprior to vaccination. Antibody titers at the mucosal surfaceranged from 1:20-1:100 while corresponding serum levels wereup to a titer of 1:12500.Conclusions: It is possible to detect vaccine-induced antibodiesagainst HIV at the mucosal surface. When antibodies are foundin the mucosa, they are at much lower titers than those seen inthe periphery.
P26.05Phase I Clinical Trial HIV-CORE002 of a UniversalT-cell Vaccine: Mapping of CD81 T Cell Epitopes
Nicola J. Borthwick1, Tina Ahmed1, Lucy Dorrell2, Andy VanHateren3, Tim Elliot3, Tomas Hanke1
1Oxford University, Jenner Institute, Oxford, United Kingdom,2Oxford University, Nuffield Department of Medicine, Oxford,United Kingdom, 3Southampton University, Southampton,United Kingdom
Background: HIV-CORE002 was a phase I clinical trial ofHIVconsv, an immunogen composed of conserved regions of theHIV-1 proteome and vectored by plasmid (DNA; D), modifiedvaccinia virus Ankara (MVA: M) and non-replicating chim-panzee adenovirus (ChAdV-63; C) in heterologous prime-boostvaccine regimens CM, DDDCM and DDDMC. The CM &DDDCM regimens were highly immunogenic and cruciallyCD8 + T lymphocytes suppressed HIV-1 replication in anin vitro virus inhibition assay. In this study we have mapped theCD8 + T cell epitopes induced by vaccination and have inves-tigated their anti-viral function.Methods: A panel of 199 15-mer peptides overlapping 11 aminoacids across the length of HIVconsv were used to identify the top5 responses per person. Panels of truncated peptides were used todefine minimal epitopes.Results: In the CM arm of the trial, we initially divided thepeptides into CD4 and/or CD8 cell subsets based on IFN-cproduction. 42.8% of the 15-mer peptides induced a singleCD8 + response and 39.2% of peptides induced responses inboth subsets. Using the participants HLA type combined withpreviously identified and/or predicted epitopes, 34 putativeCD8 + epitopes, mainly within Pol, were identified. All of theCD8 + T cells released IFN-c, TNF-a and CD107a followingpeptide stimulation indicating they are oligofunctional effectors.Restriction and anti-viral activity of selected peptides are beinginvestigated. Of particular interest was an immunodominantepitope within peptide 93 recognised by everyone sharing anHLA A02 supertype. The epitope mapped as YQYMDDLYVand is located within the active site of reverse transcriptase.Using a competition binding assay the peptide binds with highaffinity to HLA-A*02:01. Cell lines generated using peptide 93were cytotoxic against autologous peptide pulsed targets and theanti-HIV-1 activity will be presented.Conclusions: Mapping of epitopes and functionalities of cor-responding vaccine-elicited T cells will inform further vaccinedevelopment.
P26.06A Phase I Clinical Trial with a Novel gp41 HIV Vaccine(EN41-FPA2) in Healthy Female Volunteers: AMucosal Prime and Intramuscular Boost Regimen
Alethea V. Cope1, Christiane Moog2, Robin J. Shattock1, Mira M.Chawda1, Justyna Czyzewska-Khan1, Pizzoferro Kat3, SuzanneVenables1, Celine Yan1, Marie Williams3, Karen Cobb3, MahavirSingh4, Wulf Oehlmann4, Ayssar Elamin4, Dietmar Katinger5,Andreas Wagner5, Paulatsya Joshi3, David J.M. Lewis3
1Imperial College, Medicine, London, United Kingdom, 2Inserm,Strasbourg, France, 3University of Surrey, Clinical Research Centre,Guildford, United Kingdom, 4Lionex GmbH, Braunschweig, Ger-many, 5Polymun Scientific GmbH, Klosterneuburg, Austria
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