Apollo's pan-rhinovirus vaccine APL-10456 triggers cross-species T cell responses in Phase I trial
核心洞察
A single dose of APL-10456, an adjuvanted recombinant protein subunit vaccine, induced broad cross-reactive T cell responses against all three rhinovirus (搜索) species in healthy adults.
The Phase I randomized, double-blind, placebo-controlled study enrolled 144 participants, with the vaccine well tolerated and no serious adverse events reported.
APL-10456 targets a conserved protein antigen to overcome the roughly 180 genetically distinct rhinovirus (搜索) strains that have historically frustrated vaccine development.
A single dose of APL-10456, an adjuvanted recombinant protein subunit vaccine targeting rhinovirus (搜索), induced broad cross-reactive T cell responses against all three rhinovirus species in healthy adults, according to Phase I data reported by Apollo Therapeutics (搜索). The finding addresses a major obstacle that has frustrated rhinovirus vaccine development: the roughly 180 genetically distinct strains circulating across three species.
Apollo noted that rhinovirus (搜索) is responsible for an estimated 25%–50% of chronic obstructive pulmonary disease (COPD) (搜索) exacerbations and over 600,000 COPD-related hospitalizations annually in the US.
A Conserved-Antigen Strategy to Overcome Strain Diversity
APL-10456 addresses the dozens of distinct rhinovirus (搜索) strains across three species by using a conserved protein antigen with high sequence homology across strains, combined with Th1-polarizing adjuvants designed to generate CD4+ and CD8+ T cell responses that recognize peptide sequences shared across all three species. Rather than relying on neutralizing antibodies alone, the strategy targets cellular immunity to accelerate viral clearance after infection regardless of which strain is encountered.
Phase I Trial Design and Findings
The Phase I randomized, double-blind, placebo-controlled study enrolled 144 participants across two parts. Part A evaluated three single dose levels in adults aged 18–54 years. Apollo reported that a single dose was well-tolerated, induced seroconversion, and generated Th1-skewed rhinovirus (搜索)-specific cell-mediated immunity. T cell responses were detected against peptide pools representing RV-A, RV-B, and RV-C.
The most common adverse events were mild-to-moderate injection-site reactions, and no serious adverse events were reported. No quantitative immunogenicity data — such as responder rates or fold-rise in titers — were disclosed.
Part B, evaluating a two-dose regimen in adults aged 55 years and older, has completed enrollment and dosing, with results expected in Q4 2026. Apollo said it plans to initiate a randomized, double-blind, placebo-controlled Phase II trial in COPD patients in the first half of 2027.
Unmet Need in Rhinovirus-Driven Exacerbations
Existing approved therapies for COPD — including bronchodilators, inhaled corticosteroids, and biologics such as Sanofi and Regeneron's Dupixent (dupilumab) and GSK's Nucala (mepolizumab) (搜索) — address airway inflammation or selected COPD phenotypes but do not specifically target rhinovirus (搜索), while no rhinovirus vaccine or antiviral is approved. Apollo describes APL-10456 as the only vaccine in development for this indication, and the company said the Part A findings are consistent with preclinical data showing broad cross-strain immunity and rapid clearance of heterotypic rhinovirus.
Preclinical Foundation and Academic Partnership
VirTus Respiratory Research (搜索) Ltd, a specialist respiratory contract research organisation (CRO) founded by Imperial College London investigators Professor Sebastian Johnston and Dr Michael Edwards, highlighted its role in the preclinical development of APL-10456. VirTus has worked on the programme for more than five years, conducting more than 20 preclinical studies to support the selection, development and progression of the candidate, testing cross-species immunogenicity and efficacy in mouse models of rhinovirus (搜索) infection.
Professor Sebastian Johnston, Co-Founder and Chief Medical Officer of VirTus Respiratory Research (搜索), and Professor of Respiratory Medicine & Allergy at Imperial College London's National Heart and Lung Institute, said: "Rhinovirus (搜索) infections have remained an elusive target for vaccine development due to the ~180 antigenically different strains, despite the substantial burden they place on people with asthma (搜索) and COPD. After our pivotal preclinical studies at VirTus, it is hugely encouraging to see APL-10456 now generating promising clinical data in man, and we are proud to have contributed to the programme's development."
Apollo Therapeutics (搜索), headquartered in Cambridge, UK and Boston, operates a portfolio model built around academic partnerships with six leading research universities. APL-10456 sits alongside four other programs in clinical development.
Clinical Significance of Upcoming Readouts
The Part B readout in older adults will be more clinically informative than the Part A data, since the intended patient population for Phase II is adults with moderate-to-severe COPD, who are predominantly older and likely to have different immune responses to vaccination than the younger healthy volunteers in Part A.