Adjuvants Are Key to Shaping Vaccination Immune Responses

Adjuvant GLA-AF enhanced human intradermal vaccine response

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In the last 2 decades, several vaccines formulated with a new generation of adjuvants have been approved to target diseases such as influenza, hepatitis B, cervical cancer, and malaria.

Researchers say ‘adjuvants are key to shaping the immune response to vaccination.’

These vaccines could be sent through the mail as they do not require long needles or technical expertise in immunization, said researchers in a press release.

This approach represents the first adjuvanted vaccine designed for intradermal delivery, which, does not require immunization expertise (the microneedle involved is unable to penetrate deep tissue or blood vessels) and could one day be available for self-administration.

In the event of a pandemic outbreak, this approach could alleviate the congregation of patients in health centers and thus reduce the potential of these centers to enhance the spread of lethal infection.

A reliable and potent vaccine system for self-administration would provide an effective countermeasure for delivery through existing product distribution infrastructure.

In a new research study from preclinical and clinical trials that demonstrated the feasibility of an adjuvanted, intradermal vaccine that induced single shot protection in ferrets and seroprotection in humans against one of the more lethal strains of pandemic flu, Indonesia H5N1.

Rapid production and distribution of vaccines during a pandemic flu outbreak represents a critical global health challenge.

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Exacerbating matters, vaccines against flu strains with pandemic potential generally yield poor antibody responses compared to vaccines against seasonal flu strains.

Darrick Carter, a biochemist/biophysicist at the University of Washington, and the research team combined 3 technologies:

  • a hollow microneedle requiring little expertise to use,
  • noninfectious recombinant influenza virus-like particles (VLPs) that produce a stronger immune response than standard inactivated pathogens, and
  • a glucopyranosyl lipid-based adjuvant (GLA) previously shown to boost vaccine effectiveness.

In ferrets, just a single administration of the vaccine formulated in an aqueous form of the adjuvant fully protected the animals, the authors say. 

In the first-in-human trial with 100 participants, the adjuvanted vaccine, GLA-AF (aqueous formulation of glucopyranosyl lipid adjuvant), created no significant adverse effects, and, compared to controls who did not receive the adjuvanted version, those who did, showed a stronger immune response. 

The inclusion of a modern TLR4 (Toll-like receptor 4) agonist-based adjuvant was critical to the development of the response in the intradermal groups.

But to date, no adjuvant suitable for human use has been developed for intradermal vaccines.

The corresponding author’s email: [email protected]  No conflicts of interest were disclosed.