Centivax Begins Phase 1 Trial of Universal Flu Vaccine Targeting All Strains
Key Insights
Centivax (search) has initiated Phase 1a first-in-human trials of Centi-Flu 01 (search), a universal flu vaccine designed to protect against all influenza (search) strains including seasonal, pandemic, and future variants.
The vaccine uses epitope-focusing technology to target conserved viral regions (search) that cannot mutate, aiming to provide broader protection than current seasonal vaccines which are often less than 50% effective.
The Phase 1 program will enroll approximately 300 healthy volunteers across multiple hemispheres and evaluate safety and immunogenicity against a panel of 24 flu strains using established correlates of protection.
Centivax (search) has dosed the first participants in a Phase 1a clinical trial of its universal influenza (search) vaccine, marking a significant milestone in the development of a vaccine designed to protect against all flu strains rather than requiring annual reformulation. The South San Francisco-based biotechnology company announced that healthy volunteers have begun receiving Centi-Flu 01 (search) in Australia, representing the first human testing of what could become a transformative approach to flu prevention.
The Phase 1a study is a randomized, double-blind, placebo-controlled, dose escalation trial with an open-label active-controlled phase, evaluating safety and immunogenicity in healthy adults aged 18-64 and those 65 and older. Unlike conventional seasonal influenza (search) vaccines that must be reformulated annually to match predicted circulating strains, Centi-Flu 01 (search) targets conserved regions of the influenza virus that cannot mutate and are shared across strains and subtypes.
Addressing Current Vaccine Limitations
Current annual flu vaccines represent a $7 billion market but are often less than 50% effective at preventing infection. Each year, influenza (search) kills approximately 700,000 people globally, with millions of deaths occurring over the past decade. The limitations of existing vaccines stem from their reliance on predicting which strains will circulate, often resulting in mismatches between vaccine components and actual circulating viruses.
"For decades, flu vaccination has been reactive," said Sawsan Youssef, PhD, founder and Chief Science Officer of Centivax (search). "A universal influenza (search) vaccine allows us to be proactive—moving from annual guesswork to predictable durable response."
The 2025-2026 seasonal vaccines, for example, contain guidance strains from 2021, 2022, and 2023, rather than strains actually circulating in 2025-2026. This year's vaccines were particularly mismatched to the circulating Kappa "superflu," highlighting the ongoing challenge of strain prediction.
Novel Epitope-Focusing Technology
Centivax (search)'s approach represents a fundamental shift in vaccine design through its proprietary epitope-focusing technology. The platform focuses both antibody and cellular immune responses on conserved viral regions (search), creating what the company describes as a "one-two punch" of broad protection. This dual approach activates both antibodies, which serve as the body's first line of defense by blocking viral infection, and T cells, which destroy infected cells when viruses slip through initial defenses.
"The immune system doesn't fight these pathogens with one hand tied behind its back," noted Jerry Sadoff, MD, Chief Medical Officer of Centivax (search), who previously led development of vaccines including Gardasil, the shingles vaccine, and Johnson & Johnson's COVID vaccine. "Yet historically, most vaccines have focused on antibody responses and not T cell responses."
The technology has demonstrated effectiveness in extensive preclinical testing across multiple animal models including pigs, mice, rats, ferrets, and cows, as well as human organoids. In challenge studies, animals vaccinated with the universal vaccine showed protection against viruses that had evolved years after the vaccine components were designed.
Comprehensive Clinical Evaluation
The Phase 1 program will ultimately enroll approximately 300 healthy volunteers across the Northern and Southern Hemispheres. The current Phase 1a trial in Australia takes advantage of the Southern Hemisphere's summer season to avoid confounding effects from circulating flu viruses. A Phase 1b trial is planned for the Northern Hemisphere during summer 2026 in the United States, United Kingdom, and potentially the Netherlands.
The study will evaluate efficacy using the gold-standard hemagglutination inhibition (HAI) assay against a panel of more than 24 flu strains, including currently circulating strains, historical mismatch strains, seasonal guidance strains, and pandemic strains like H5N1. This represents a significant expansion from conventional vaccine testing, which typically evaluates only against three guidance strains.
"We are aiming to correct the problem so many of us experience: where, despite taking a flu shot, you still get sick," said Jacob Glanville, PhD, founder and Chief Executive Officer of Centivax (search). "The Phase 1A is a key value-inflection point for the company because we will see very quickly whether the vaccine—and the universal immunity platform—is working and if it outperforms standard of care."
Broader Platform Applications
Beyond influenza (search), Centivax (search)'s universal immunity platform is advancing multiple programs including a pan-herpes Alzheimer's preventative, a broad oncology treatment, a malaria (search) vaccine, and a universal antivenom recently published in Cell. The platform's versatility stems from its ability to identify and target conserved regions across diverse pathogens.
"Vaccines can deliver benefits well beyond preventing the initial infection, serious disease and symptom reactivation caused by pathogens," Sadoff explained, referencing emerging evidence that shingles vaccination is associated with lower risks of Alzheimer's disease (search) and cardiovascular events. "We believe universal vaccines can take this further—expanding protection across diverse pathogens as well as protecting against the diverse long-term pathology they contribute to."
Strong Financial Backing
The company has secured over $26 million in non-dilutive financing from organizations including the Bill & Melinda Gates Foundation, the Coalition for Epidemic Preparedness (CEPI), the National Institutes of Health (NIH), the United States Department of Agriculture (USDA), and various Department of Defense entities. Private investors include Future Ventures (search), NFX (search), Global Health Investment Corporation (GHIC), BOLD Capital Partners, and others.
The Gates Foundation awarded Centivax (search) a "Grand Challenge: End the Pandemic Threat" grant in 2019 based on early pig study data that demonstrated universal immune responses. This recognition helped accelerate additional studies in the United States using pigs and ferrets, which continued to show strong protective effects against diverse viral strains.
First data from the 180-subject Phase 1a trial is expected within the year, with results potentially demonstrating whether this universal approach can achieve the 85-95% efficacy rates associated with vaccines like tetanus, rather than the variable effectiveness of current flu vaccines.