TBA (16S127)

CO-ADMINISTRATION OF CHIMPANZEE ADENOVIRAL VECTORS OF DIFFERENT SEROTYPES, FOR THE PREVENTION OF HCV AND HIV CO-INFECTION.

Author(s)

Felicity Hartnell (1) , Anthony Brown (1) , Emma Ghaffari (2) , Beth Turner (2) , Antonella Folgori (3) , Stefania Capone (3) , Alfredo Nicosia (3) , Riccardo Cortese (3), Stefano Colloca (3) , Tomas Hanke (4) , Lucy Dorrell (2) , Ellie Barnes (1)

Department(s)/Institutions

1 Peter Medawar Building, 2 NDM Research Building, University of Oxford, Oxford, United Kingdom, 3 ReiThera Srl, Rome, Italy, 4 Jenner Institute, University of Oxford, Oxford, United Kingdom preprocess

Introduction

An estimated 5-7 million people globally are co-infected with HIV-1 and HCV. HCV is the leading cause of non-AIDS deaths in co-infected individuals. New antiviral therapies, although promising, are unaffordable to most and do not prevent reinfection. .

Aims/Background

We have developed a novel vaccination strategy employing replication-defective serologically distinct chimpanzee adenovirus (AdCh3, and ChAdV63) for the simultaneous delivery of HCV non-structural (NSmut) and HIV-1 conserved (HIVconsv) region immunogens. Priming vaccination is followed by heterologous MVA vectored boost with the aim of inducing potent HIV and HCV specific T cells responses in healthy volunteers.

Method

32 healthy volunteers were recruited in a Phase-I (EU Fp7 funded) clinical trial and sequentially enrolled into 3 groups: Group 1 (n=8) received HCV vaccines: AdCh3NSmut1 [2.5x10e10 vp] and MVA.NSmut [2x10e8 pfu] at weeks 0 and 8 and respectively. Group 2 (n=8) received HIV vaccines: ChAdV63.HIVconsv and MVA.HIVconsv at the same interval [ 5x10e10 vp and 2x10e8 pfu respectively]. Group 3 (n=16) were co-primed with AdCh3NSmut1 and ChAdV63.HIVconsv (dosed as previous) followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1x10e8 pfu]. All vaccines were given i.m.. Immunogenicity was determined using peptide pools in ex-vivo IFN-y ELISpot assays.

Results

Vaccine priming with either AdCh3NSmut or ChAdV63.HIVcons alone induced high magnitude and broad peak T cell responses (mean ± SD: 608.5 ± 374 and 785 ±753 SFU/10e6 PBMC respectively) and responses were markedly enhanced following heterologous MVA boost (peak mean 4260 ±2390 and 3760 ±2811 SFU/10e6 PBMC targeting NSmut and HIV cons respectively). Co-administration of AdCh3NSmut1 and ChAdV63.HIVconsv did not impair the magnitude or breadth of either HCV or HIV specific T cell responses compared to each alone; peak ELISpot responses to the HCV immunogen prime and boost vaccines were 1184 ± 869 and 5297 ± 3153 SFU/10e6 PBMC respectively, and to the HIV immunogen 780 ± 774 and 3081 ± 3724 SFU/10e6 PBMC respectively. All vaccines were well tolerated with no serious AE’s.

Conclusions

Coadministration of serologically distinct adenoviral vectors encoding HCV and HIV-1 immunogens in a heterologous prime-boost regimen can be safety administered and induce broad and high magnitude T cell responses. This provides a novel strategy for the prevention of multiple pathogens in the same individual. preprocess