Gut microbes and the quest for needle-free vaccines

by Luisa Torres

A new vaccination method may spare us the needles and the pain,  but it may not work as well in people who are obese or in those whose gut bacteria are different due to antibiotic use, researchers from Cornell University reported last month in the Journal of Science Advances.

Although vaccines have saved more lives than any other medical invention, the need for multiple shots, people’s fear of needles, and the limited effectiveness of some vaccines has encouraged research on different methods of vaccine delivery. Poly (lactic-co-glycolic acid) (PLGA) particles have emerged as a possible alternative, particularly because they seem to increase vaccine efficacy. However, our gut bacteria might dictate whether this new method of vaccine delivery can effectively protect us from disease, according to new research.

Vaccines train our immune system to fight infections. They are composed of dead or weakened versions of pathogens that “teach’ the immune system how to get rid of them once the body encounters the real thing. Vaccines typically contain one or more adjuvants or enhancers which increase the efficacy of the vaccine by boosting the response of the immune system.  In contrast, nanovaccines use nanoparticles that carry synthetic versions of pathogens and strongly activate the immune system without the need for adjuvants. Because pathogens and nanoparticles have a similar size, this results in better stimulation of the immune system and increased vaccine efficacy. Nanovaccines are more stable in the blood compared to traditional vaccines. They don’t require refrigeration which lowers their cost and facilitates access. They eliminate the need for booster doses and are also painless and needle-free, as they can be delivered intranasally or orally.

Despite the added benefits, nanovaccines may not be for everyone. Most preclinical studies that examine the efficacy of nanovaccines have been done in healthy mice, without consideration for comorbidities or other factors that may affect the outcome of vaccination. This is an important variable to consider, as it may limit the effectiveness of some vaccines in some individuals.

The researchers tested the efficacy of nanovaccines containing PLGA particles on mice lacking TLR5, a protein present in the gut that helps our bodies defend against infection. These mice have altered microbiomes and develop characteristic symptoms of metabolic syndrome, a cluster of conditions that together increase the chance of type 2 diabetes, heart disease, and stroke. These symptoms include high fat content in the blood, high blood pressure, insulin resistance, and increased body fat.

Mice with metabolic syndrome responded less to vaccines compared to healthy mice. Wild-type mice and mice lacking TLR5 were vaccinated with PLGA nanoparticles. Only the wild-type mice had increased numbers of B cells in the lymph nodes as well as increased numbers of macrophages and dendritic cells circulating in their system, an indication  that the vaccine was working and activating the immune system only in wild-type mice but not in the animals lacking TLR5.

To test whether an altered microbiome was enough to reduce vaccine efficacy independently of metabolic syndrome, the researchers exposed wild-type mice to the antibiotics ampicillin and neomycin in their drinking water for 16 weeks. Simply perturbing the microbiome led to a reduced efficacy of the PLGA nanovaccine. Microbiome analysis before immunization showed that antibiotic-treated wild-type mice had a significant decrease in several types of gut bacteria, including Bacteroidetes, Firmicutes, and Actinobacteria and an increase in Proteobacteria. After immunization, mice exposed to antibiotics did not show signs of a stimulated immune system, as evidenced by unchanged numbers of B cells, dendritic cells, and macrophages, as well as unchanged levels of pro-inflammatory cytokines in the serum.

Even though mice lacking TLR5 showed signs of reduced vaccine efficacy, not everything was lost for them. The researchers showed that a different type of nanovaccine stimulated their immune system just as well as the PLGA nanovaccine had done in the wild-type mice. They used pyridine–poly (hydroxyethyl methacrylate) (Pyr-pHEMA), where pyridine is an aromatic compound that activates immune cells through TLR2 but not TLR5. The researchers showed that immunization with Pyr-pHEMA led to a significant stimulation of immune cells in the mice lacking TLR5, who showed increased B cells in the lymph node and increased numbers of circulating macrophages and pro-inflammatory cytokines.

This study shows the potential to use different nanomaterials that can be customized according to the health of the patient and other characteristics. It may overcome current limitations of vaccines including painful shots and reduced efficacy in some cases. Maybe one day injected vaccines and booster shots will be a thing of the past and painless, more effective vaccines will be a reality.



About the Author

Luisa Torres is a Senior Consultant and Life Science Proposal Development Specialist at Intelispark. She has a PhD in Pharmacology from Stony Brook University. You can find her on twitter as @luisatorresduq and in instagram as @nailsciart

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