ADJUVANTS

Adjuvants are substances added to vaccines that enhance the ability of antigens to stimulate the body’s immune response. Adjuvants provide a key benefit to vaccine development by:

  • Improving immune response
  • Broadening vaccine protection
  • Reducing the amount of antigen needed

IDRI is a world leader in adjuvant development and has developed multiple adjuvant formulations. In addition to vaccines that we are developing for tuberculosis, leprosy and leishmaniasis, we are also working with collaborators to provide adjuvants for vaccines they are developing in various disease areas, including malaria, HIV/AIDS and pandemic flu.

CHALLENGE

©Earl HarperWhile vaccines have proven to be effective in controlling and eliminating infectious diseases, few new effective vaccines have been recently developed. Many diseases either have no vaccines or vaccines that are not effective. If we could protect the global population from infectious diseases such as tuberculosis, HIV/AIDS and the malaria through vaccination, we could dramatically advance global health and reduce the health care costs that burden many governments.

SOLUTION

In the past, many vaccines were developed using weakened or dead pathogens. However, most vaccines developed today – called subunit vaccines – include only specific parts of the pathogen that are most recognizable to the human immune system rather than the entire virus or bacteria. These vaccines, which are the type IDRI scientists are focusing on, have two main components:

  • Antigens stimulate antibodies in the immune system to combat infectious diseases.
  • Adjuvants are ingredients in a vaccine that helps create a stronger immune response, making the vaccine work better. The word “adjuvant” comes from the Latin word adiuvare, meaning “to help.” Adjuvants have been used safely in vaccines for decades.

Adjuvants are an important part of an outbreak response, as they can dramatically increase vaccine availability. IDRI’s adjuvants can be used to increase the number of available vaccine doses through “dose sparing,” reducing the amount of vaccine antigen needed per individual dose. This allows more vaccine doses to be available, stretching vaccine manufacturing capacity to help protect more people.

Patra K, Li F, Carter D, Gregory J, Baga S, Reed SG, Mayfield S, and Vinetz J, Algae-produced malaria transmission-blocking vaccine candidate Pfs25 formulated with a human use-compatible potent adjuvant induces high affinity antibodies that block Plasmodium falciparum infection of mosquitoes” Infect Immun. 2015 May;83(5):1799-808. doi: 10.1128/IAI.02980-14. Epub 2015 Feb 17

Desbien AL, Reed SJ, Bailor HR, Cauwelaert ND, Laurance JD, Orr MT, Fox CB, Carter D, Reed SG, Duthie MS. Squalene emulsion potentiates the adjuvant activity of the TLR4 agonist, GLA, via inflammatory caspases, IL-18, and IFN-γ. Eur J Immunol. 2015 Feb;45(2):407-17. doi: 10.1002/eji.201444543. Epub 2014 Dec 3. PubMed PMID: 25367751.

Arias MA, Van Roey GA, Tregoning JS, Moutaftsi M, Coler RN, Windish HP, Reed SG, Carter D, and Shattock RJ “Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 Agonist, Promotes Potent Systemic and Mucosal Responses to Intranasal Immunization with HIVgp140” PLoS One. 2012;7(7):e41144. Epub 2012 Jul 19. PMID: 22829921; PubMed Central PMCID: PMC3400629.

Wiley SR, Raman VS, Desbien A, Bailor HR, Bhardwaj R, Shakri AR, Reed SG, Chitnis C, Carter D “Targeting TLRs Expands the Antibody Repertoire in Response to a Malaria Vaccine” Science Trans. Med. 2011 Jul 27;3(93):93ra69. doi: 10.1126/scitranslmed.3002135.

Fox, C. B; Barnes V, L.; Evers, T.; Chesko, J. D.; Vedvick, T. S.; Coler, R. N.; Reed, S. G.; Baldwin, S. L. “Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy,” Influenza and Other Respiratory Viruses, 2013, 7:815-826.

Fox, C. B.; Huynh, C.; O’Hara, M. K.; Onu, A. “Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania,” Vaccine, 2013, 31:1633-1640.

Reed, S. G.; Orr, M. T.; Fox, C. B. “Key roles of adjuvants in modern vaccines,” Nature Medicine, 2013, 19:1597-1608.

Fox, C. B.; Moutaftsi, M.; Vergara, J.; Desbien, A. L.; Nana, G. I.; Vedvick, T. S.; Coler, R. N.; Reed, S. G. “TLR4 ligand formulation causes distinct effects on antigen-specific cell-mediated and humoral immune responses,” Vaccine, 2013, 31:5848-5855.

Misquith, A.; Fung, H. W. M.; Dowling, Q. M.; Guderian, J. A.; Vedvick, T. S.; Fox, C. B. “In vitro evaluation of TLR4 agonist activity: formulation effects,” Colloids and Surfaces B: Biointerfaces, 2014, 113:312-319.

Fox, C. B.; Sivananthan, S. J.; Duthie, M. S.; Vergara, J.; Guderian, J.A.; Moon, E.; Coblentz, D.; Reed, S. G.; Carter, D. “A nanoliposome delivery system to synergistically trigger TLR4 and TLR7,” Journal of Nanobiotechnology, 2014, 12:17.

Fox, C. B.; Mulligan, S.; Sung, J.; Dowling, Q. M.; Fung, H. W. M.; Vedvick, T. S.; Coler, R. N. “Cryo-transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes,” International Journal of Nanomedicine, 2014, 9:1367-1377.

TECHNOLOGY TRANSFER

We are enabling worldwide access to our immune-enhancing technologies. IDRI has transferred its adjuvant technologies to Romania, Brazil and India, where we teach scientists and engineers how to manufacture adjuvants for their own vaccines.

©Earl HarperIn one of IDRI’s latest tech transfer projects, we are partnering with developing country vaccine manufacturers (DCVMs) to develop adjuvanted influenza vaccine capabilities. IDRI will supply sufficient oil-in-water emulsion adjuvant and partner with up to two DCVMs to enhance their pandemic influenza vaccine programs. These adjuvants will be evaluated with antigen through preclinical and clinical studies.

As part of this project, IDRI will establish the capacity to manufacture 50 million doses of adjuvant within a three-month timeframe, to provide adjuvants to eligible DCVMs supported through the World Health Organization (WHO) Global Action Plan for Influenza Vaccines.