A Fresh Look at Vaccines

Returning to First Principles

Clarus Biologics, Inc.

Clarus Biologics is developing a two component vaccine strategy.

Component One:

A virus-like particle (VLP) which sends a strong non-specific activation signal to the immune system, just like a real infection.

Component Two:

Co-administered, pathogen-specific antigenic mass in the form of recombinant protein(s), pathogen subunit(s) or an inactivated pathogen.

Combines the best qualities of live attenuated vaccines and inactivated or recombinant vaccines.

  • Rapid production of full and complete immune responses: antibodies, T-cells and mucosal immunity, even after non-mucosal immunization.
  • Protection against infection, disease, death and transmission to others.
  • Long-lasting immunity.
  • Safety.
  • Rapid vaccine development timelines.
  • Ability to utilize VLP with selected existing commercial vaccines.
  • Ability to independently optimize a) activation of the immune system and b) antigenic mass for maximum vaccine efficacy.
  • Compatible with multivalent vaccines, either against multiple variants of the same pathogen or multiple pathogens.
  • Improved safety profile compared with live attenuated vaccines.
  • Reduced cost and increased efficacy compared with inactivated or recombinant vaccines.

Ideal design for pandemic preparedness.

  • The non-specific VLP component can be stockpiled.
  • The pathogen-specific component can be rapidly produced after identification of the causative organism and added to the stored VLP component in simple aqueous suspension.

Rationale for the Clarus approach.

How did our immune systems evolve?

  • Our immune systems evolved to respond to target elements of infectious pathogens (usually proteins, designated as antigens) in the context of a contemporaneous infection.
    During an infection, the immune system:
  • Recognizes that an infection has occurred,
  • Responds rapidly and specifically to the infecting pathogen with all elements of the adaptive immune system, including pathogen-specific antibodies, T-cells and mucosal immunity,
  • Stops disease progression,
  • Clears the pathogen from the body, and
  • Establishes immunologic memory, often life-long, to prevent future infection, disease and transmission of that same pathogen to others.

Why don’t our immune systems respond to everything?

  • If we respond to elements of our own bodies, we get autoimmune diseases.
  • If we respond to things we eat and breathe, we get allergies.

The immune system has evolved to respond to pathogens during a contemporaneous infection. It also has co-evolved to NOT respond to foreign environmental antigens in the absence of infection.


Induce a full and complete anti-pathogen immune response in the absence of a contemporaneous infection.


Make the immune systems of vaccine recipients think they have been infected while simultaneously administering immunizing vaccine antigens.

What historical vaccination strategies work best?

Infection with the target pathogen.

The first persons successfully vaccinated against a pathogen were those who survived an infection with that pathogen. (An approach not highly favored by FDA.)

Vaccination with a closely related organism.

Animal pathogens which do not cause symptomatic human disease, but which nevertheless grow to a limited extent in humans and are sufficiently similar to the human pathogen to induce protective immunity. (e.g. vaccines against smallpox, rotavirus)

Live attenuated vaccines.

Versions of a pathogen with mutations allowing asymptomatic growth in the body sufficient for immunization against the actual pathogen. (e.g. vaccines against measles, mumps, rubella)


What do these most effective vaccines have in common?

  • They are infections and are seen as such by the immune system.
  • They produce antigenic mass in the body sufficient for effective immunization.

How will the two component Clarus Biologics vaccine design produce these desirable properties?

  • They are infections and are seen as such by the immune system.
  • They produce antigenic mass in the body sufficient for effective immunization.

Component One (Clarus VLP):

  • A highly mutated non-pathogenic VLP, which can complete only the first steps of an authentic virus infection of dendritic cells in the lymph nodes draining the site of inoculation.
  • Genetically unable to produce additional VLP in the body.
  • Sends the same authentic signals to the adaptive immune system as a real infection.
  • These signals interpreted in the body as an active infection requiring an immediate, high level immune response to co-administered antigens.

Component Two:

  • Recombinant protein, pathogen subunit or killed pathogen provides specificity and antigenic mass.
  • Co-administered with Clarus VLP such that both migrate to the same draining lymph nodes.

The Clarus VLP + co-administered antigen make vaccine recipients respond immunologically as if they were infected with a real pathogen or a live attenuated vaccine, thus producing a maximal response.

Will Clarus Biologics vaccines work?

In animal models, the success of the Clarus vaccine design has been strongly demonstrated.

A commercial influenza vaccine (a source of influenza subunit antigen) was given to groups of monkeys with or without the Clarus VLP.  After two inoculations, the animals that received VLP+vaccine produced over 20 times the antibody produced by the monkeys that received the same dose of commercial vaccine alone.  When challenged in the nose with infectious influenza, the VLP+vaccine animals were completely protected, a significant improvement over not only saline controls but also over vaccine alone.  These findings were confirmed in additional primate studies, and multiple other successful studies in rodent models.

In humans, success of the Clarus vaccine design is anticipated in that:

  • The Clarus vaccine design was strongly protective in nonhuman primates.
  • The Clarus VLP can infect cultured primary dendritic cells derived from human blood samples.

Next Steps:

Demonstrate the superior efficacy of the Clarus vaccine design

  • Produce clinical grade Clarus VLP under FDA-mandated current Good Manufacturing Practices (cGMP).
  • Conduct a Phase I clinical trial in humans comparing safety and efficacy of commercial influenza vaccine alone with the same vaccine mixed with Clarus VLP. A third arm of the trial will examine Clarus VLP alone.