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  • Writer's pictureP.K. Peterson

New Approach to Antimicrobial Resistance: “Stimulate the Phagocytes”

“There is at bottom only one genuinely scientific treatment for all diseases, and that is to stimulate the phagocytes, drugs are a delusion.”

-  Sir Colenso Ridgeon (character in George Bernard Shaw’s The Doctor’s Dilemma, 1906)

“It’s like Homeland Security putting out a terror alert. You’re alerting the soldiers and tanks of your immune system.”

-  Brad Spellberg, M.D., chief medical officer, Los Angeles County-University of Southern California Medical Center

Vaccines are the linchpin of prevention of infectious diseases. All current vaccines are given to enhance immune memory. This is called adaptive immunity. In this week’s Germ Gems post, I highlight a highly innovative vaccine approach aimed at stimulating the innate immune system. Scientists hope that this approach can protect people from what is considered by many public health experts the greatest infectious disease threat of our time—infections caused by antibiotic-resistant microbes (ARM). (November 18-24 is “World AMR Awareness Week.”)

Anatomy of the immune system. The immune system is exquisitely orchestrated to protect the body against foreign invaders, namely microbes, as well as against cells that have gene mutations, namely cancer cells. An overly simplistic view of the immune system organizes it into an adaptive immune system (comprised of T and B lymphocytes and their products) and an innate immune system (neutrophils, macrophages, NK cells, and complement proteins).

We rely on the adaptive immune system to develop memory of specific pathogens that have infected us previously or that we’ve been exposed to by a vaccine containing a weakened form of the pathogen or its components (antigens). But this process takes time. Thus, when we have an acute infection, we depend on the “battle ready” cells of the innate immune system to eliminate all sorts of newly encountered pathogens in a non-specific manner. Phagocytes (the body’s white blood cells—neutrophils and macrophages) are essential contributors to the innate immune system. They protect the body by ingesting foreign invaders (bacteria) and dead or dying cells. (In 1881, the Ukrainian zoologist Elie Metchnikoff discovered the pivotal role phagocytes play in immunity.)

Vaccination to protect against AMR organisms. The field of vaccinology can be traced to the 15th century when dried crusts from smallpox lesions were used to prevent this devastating viral infection. Historically, vaccines have been developed to target specific (single) pathogens. The vaccines work by enlisting the adaptive immune system to remember these pathogens, or their components.

This strategy has worked remarkably well against specific pathogens. Two examples are the vaccine-induced eradication of smallpox in 1980, and, most recently, the COVID-19 vaccines that saved millions of lives.

Antibiotic-resistant microbes (ARMs) are a challenge for this targeted approach to protection. Why? In part, because there are just too many ARMs including many gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and even a fungus, Candida species. (I reviewed the scope of the antimicrobial resistance problem in my April 13, 2022 Germ Gems post, “Antimicrobial Resistance: the Elephant in the Pandemic Room.”)

Recently, however, scientists at the University of Southern California (USC) demonstrated an exciting new approach for solving the ARM problem—stimulate the innate immune system. Dr. Brad Spellberg and his USC colleagues used a vaccine containing three substances known to boost general immune responses (aluminum hydroxide, monophosphoryl lipid A, and glucan particles). When given to mice several days before exposure to ARMs, the vaccine protected against death caused by bloodstream infection by MRSA and other AMR pathogens.

Spellberg and his colleagues published the results of their study on October 4, 2023 in Science Translational Medicine. The exact mechanism by which their vaccine works is still unknown. (For example, does it stimulate NK cells as well as phagocytes [neutrophils and macrophages] or other members of the immune system.) Yet, in the October 5, 2023 issue of Drug & Medication News, Health & Medical News, their findings were described in the article “New Vaccine Blocks All Hospital Superbugs—Turns Immune System Into The ‘Incredible Hulk.’”

There is a long way to go before we see the results of human trials using this novel approach. Nonetheless, stimulating the innate immune system is a promising new direction in vaccine development. And, it just may be what we need in our battle against AMR microbes.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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