PVX108 – A Peptide Immunotherapy for Peanut Allergy Safely Induces Durable Immune Changes in Peanut-Allergic Adults
A. Voskamp1, 2, 3, 4; S. Khosa5; H. Deberg5; J. Rolland4; R. O'hehir3, 4, 2; P. Hickey2; E. Wambre5; S. Prickett2, 4, 3
1White Fox Scientific Consulting, Nelson, New Zealand; 2Aravax, Melbourne, Australia; 3The Alfred, Melbourne, Australia; 4Monash University, Melbourne, Australia; 5Benaroya Research Institute, Seattle, United States of America
Background

Food allergy is a leading cause of anaphylaxis worldwide. Allergen-specific immunotherapy is the only treatment shown to modify the natural course of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions during treatment and requirement for indefinite daily dosing. PVX108 is a peptide-based immunotherapy designed to suppress peanut allergy through T cell modulation via a series of monthly injections, without triggering allergic reactions during treatment.

We previously reported safety and tolerability of PVX108 in a randomized, double-blind, placebo-controlled Phase 1 trial in peanut-allergic adults, and shared some preliminary immunological data from these participants. Here we extend these investigations to present more detailed immunological analyses on this cohort.

Method

Peanut allergic adults each received six injections of PVX108 (n=10) or placebo (n=5) over 16 weeks.  Peanut-reactive CD4+ T cell phenotyping (including RNA sequencing), titrated peanut skin prick testing, and peanut-specific serum IgE and IgG4 levels were assessed at predose, Week 21 (1 month post treatment), and Month 18 (14 months post-treatment).

Results

Peanut-reactive memory Th2(A) cells expressing markers associated with allergic inflammation decreased significantly at Month 18 compared to predose and Week 21 in the PVX108 group compared to placebo. Peanut-reactive T cells expressing markers associated with suppressor function increased in the PVX108 group compared to placebo by Month 18 compared to pre-dose. These included a population of CCR6+ Th17-like Th cells expressing FOXP3 and a population of conventional regulatory T cells (CD154-/CD137+/CD25+/CD27-) expressing GARP and LAP.

T cell changes were apparent by Week 21 but became more pronounced by the Month 18 timepoint. These changes were followed by evidence of increased peanut specific IgG4 and reduced peanut SPT responses at Month 18 compared to pre-dose in the PVX108 group, but not placebo. 

Conclusion

The observed combination of directional changes was consistent with the anticipated mechanism of action for PVX108 and has been associated with clinical benefit in other studies of specific immunotherapy for allergy (including peanut). These data demonstrate potential for PVX108 to safely induce long-lasting modulation of peanut-specific immune responses in peanut-allergic individuals.