As our understanding of immunity deepens, our repertoire of immune modulators expands so that we can influence our immune defenses in a beneficial direction. The vaccine company Novavax, in working on a COVID-19 vaccine, has incorporated saponins from Chilean soapbark trees into their vaccine with the goal of boosting both antibody and cell-based immunity. Whereas traditional vaccines stimulate antibody or humoral immunity, a vaccine that stimulates T cells in our immune systems may lead to a more effective vaccine.
For those skeptical of vaccine adjuvants, one questions arises whether a particular direction is truly beneficial or ultimately harmful. Adjuvants, or substances which augment an immune response to a vaccine, are added by vaccine creators to make the vaccine stronger in eliciting an immune response and therefore more effective. Many express doubts about the safety of the commonly used adjuvants aluminum and squalene, hoping research will uncover adjuvants that are more clearly proven to be safe. Vaccines do no have to be inherently risky if time and effort is put into making both the microbial antigen and the adjuvants both safe.
Novavax looks to nanoparticle technology for such an effective and safe vaccine adjuvant. Technology for producing saponin nanoparticles has been around since 1982 when it was first produced. This technology simply produces liposomal, or fatty based, microscopic particles when facilitate the entry of their enveloped package into cells and activation of the immune response. In the case of vaccines, the liposomal nanoparticles deliver the protein intended for immune recognition to the immune system for processing. In many oral therapies used in functional medicine, liposomal nanoparticles from soy or sunflower lecithin assist nutrients to pass through the intestine into the bloodstream.
Saponin, the active component of the vaccine nanoparticle, originates in the bark of Chilean soapbark trees. In one form it can be toxic, but when processed into nanoparticles, it can be safe yet still stimulate an immune response. The saponin is mixed in a certain manner with cholesterol and phospholipids to create the nanoparticles. The shingles vaccine already uses this type of nanoparticle adjuvant. Other companies either utilize this adjuvant technology or are researching it for future vaccines.
The mechanism of action for these somewhat natural adjuvants crosses several areas of immunological activity. The saponins can stimulate cytokine responses which boost both the Th1 cell mediated arm and the Th2 antibody mediated arm of the immune system. In some research they seem to improve the mobilization of immune cells in the lymph nodes around the injection site. They also stimulate general inflammation through inflammasomes, protein units in immune cells that trigger an inflammation cascade.
This scientific explanation of Novavax’s attempts at a COVID vaccine using saponin adjuvants then deserves some further explanation regarding why their vaccine has not hit the market yet in the US. With 3 available vaccines which are getting some negative press in regards to their efficacy and safety, why has Novavax’s version with reported efficacy studies not received approval? We can all theorize why there has been a delay despite some approval by a few foreign countries, but at least part of it results from slow production ability from the small company. The article from the British Medical Journal offers some reasonable background if you want to know more.
As we look to 2022 and beyond, understanding the basics of vaccines and their adjuvants is important if we are to choose as a society which responses to infectious threats are the best. While not everyone needs to enter an immunology program for their PhD, we should all take a few minutes to recognize possible mechanisms by which we can enhance or hinder our immune system. The reality of our fallen world means that we will face infections and need strong immune systems. Functional medicine would argue that the best immune defense begins with optimizing nutrition, minimizing toxins, and understanding the battle with our microbial foes. From there we can then choose wisely which chemicals from the pharmaceutical world enter our mouths or our bodies.
Bibliography:
Murillo Silva, Yu Kato, Mariane B. Melo, Ivy Phung, Brian L. Freeman, Zhongming Li, Kangsan Roh, Jan W. Van Wijnbergen, Hannah Watkins, Chiamaka A. Enemuo, Brittany L. Hartwell, Jason Y. H. Chang, Shuhao Xiao, Kristen A. Rodrigues, Kimberly M. Cirelli, Na Li, Sonya Haupt, Aereas Aung, Benjamin Cossette, Wuhbet Abraham, Swati Kataria, Raiza Bastidas, Jinal Bhiman, Caitlyn Linde, Nathaniel I. Bloom, Bettina Groschel, Erik Georgeson, Nicole Phelps, Ayush Thomas, Julia Bals, Diane G. Carnathan, Daniel Lingwood, Dennis R. Burton, Galit Alter, Timothy P. Padera, Angela M. Belcher, William R. Schief, Guido Silvestri, Ruth M. Ruprecht, Shane Crotty, Darrell J. Irvine. A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity. Science Immunology, 2021; 6 (66) DOI: 10.1126/sciimmunol.abf1152
Sharma, Rinku et al. “Exploring the possible use of saponin adjuvants in COVID-19 vaccine.” Human vaccines & immunotherapeutics vol. 16,12 (2020): 2944-2953. doi:10.1080/21645515.2020.1833579
Tinari S, Riva C. Covid-19: Whatever happened to the Novavax vaccine? BMJ 2021; 375 :n2965 doi:10.1136/bmj.n2965
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