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By Clare Fleishman, MS, RD, for the International Probiotics Association 

 

As the world awaits a vaccine for SARS-CoV-2, the question arises: Will it be equally effective for everyone? 

If other vaccines are predictive, the answer is an unequivocal “no.” Public health researchers know that individual immune response to vaccinations can vary greatly — for a multitude of reasons.  

Improving vaccines’ efficacy may save lives. One area of interest is the gut microbiota, its influence on vaccine response and the potential for probiotics to act as immunologic modulators as well as adjuvants. [/vc_column_text][vc_column_text css=".vc_custom_1605291984178{border-top-width: 5px !important;border-right-width: 5px !important;border-bottom-width: 5px !important;border-left-width: 5px !important;padding-top: 5px !important;padding-right: 5px !important;padding-bottom: 5px !important;padding-left: 5px !important;background-color: #ffeaea !important;border-left-color: #dd3333 !important;border-left-style: solid !important;border-right-color: #dd3333 !important;border-right-style: solid !important;border-top-color: #dd3333 !important;border-top-style: solid !important;border-bottom-color: #dd3333 !important;border-bottom-style: solid !important;border-radius: 1px !important;}"]

Vaccines, A Snapshot

As defined by the CDC, a vaccine is a product that stimulates a person's immune system to produce immunity to a specific disease, protecting the person from that disease. The smallpox vaccine was the first vaccine to be developed, back in 1796. Since then, numerous vaccines have been deployed against life-threatening diseases. Immunization currently prevents 2-3 million deaths every year from diseases like diphtheria, tetanus, pertussis, influenza, and measles.

According to the excellent New York Times Tracker, researchers are currently testing (this is fluid) 48 vaccines for SARS-CoV-2 in clinical trials on humans, and at least 89 preclinical vaccines are under active investigation in animals.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_column_text]

Vagaries of vaccines  

As outlined in a 2019 review article, vaccine responses can be influenced by these factors:  

• Intrinsic (age, sex, genetics, and comorbidities) 
• Perinatal (gestational age, birth weight, feeding method, and maternal factors) 
• Extrinsic (preexisting immunity, microbiota, infections, and antibiotics) 
• Environmental (location, season, family size, and toxins) 
• Behavioral (smoking, alcohol consumption, exercise, and sleep) 
• Nutritional (body mass index, micronutrients, and enteropathy)  
• Vaccine (type, product, adjuvant, dose, schedule, site, route, time and co-administered vaccines and drugs) 

Resulting variations in vaccine response can be stark, as is seen in differences in low- to middle-income countries (not as effective) as compared to high-income countries. Optimizing vaccine success is a primary public health goal in all countries across the globe. 

In this article, we will look first at how the microbiota may influence vaccine response and then explore if probiotics in altering microbiota may impact vaccine response or act effectively as adjuvants.  

 

Microbiota influence vaccine response 

The gut microbiota and the immune system have a bidirectional relationship: The microbiota impacts the immune system, which in turn contributes to microbial homeostasis. This elegant interplay can be a factor in vaccine responses.  

Intestinal disturbance or dysbiosis is thought to be a factor in poor oral vaccine response in children from low-income countries. Diet, delivery method, and sanitation can alter the microbiome. Also, breastfeeding may modulate vaccine responses in infants via altering the microbiome composition and maternal antibody interference with the development of the active (post-vaccine) immune response.  

Alterations in the intestinal microbiota are now recognized as a leading factor associated with vaccine failures, and their effects are being evaluated in both pre-clinical and clinical studies as shown in this Table.  

Animals Impaired antibody responses to influenza vaccine have been seen in germ-free or antibiotic-treated animals. Also dietary fiber has been observed to play a positive role in an effective immune response and is likely related to the fermentation products produced by the microbiota. 

Humans A recent review by researchers Petra Zimmermann and Nigel Curtis in Australia summarized four clinical studies (three in infants and one in adults): “All found an association between the intestinal microbiome and vaccine responses…findings across studies were consistent: a higher relative abundance of the phylum Actinobacteria (oral and parenteral vaccines) and Firmicutes (oral vaccines) was associated with both higher humoral and higher cellular vaccine responses, while a higher relative abundance of the phylum Proteobacteria (oral and parenteral vaccines) and Bacteroidetes (oral vaccines) was associated with lower responses.”  

Details are included in Table 12 of the review.  

 

Potential probiotic impact on vaccine response 

The effects of probiotics on vaccine responses are detailed in another recent review by Zimmerman and Curtis. The researchers found 26 prospective randomized placebo-controlled studies in humans involving 3812 participants, investigating the effect of 40 different probiotic strains on the response to 17 different vaccines.    

The authors wrote: 

“A beneficial effect of probiotics was reported in about half of the studies. The evidence for a beneficial effect of probiotics on vaccine response was strongest for oral vaccinations and for parenteral influenza vaccination. However, there was substantial variation between studies in the choice of probiotic, strain, dose, viability, purity, and duration and timing of administration." 

These variations may have led to a recent meta-analysis showing “no significant benefits overall for probiotics, despite findings from individual studies that probiotics can increase levels of specific antibodies to oral vaccines.” 

Nevertheless, mechanisms of probiotic action in vaccine performance have yet to be elucidated; however both direct and indirect pathways have been proposed. 

 

Probiotics as potential adjuvants 

Adjuvants are used in conjunction with vaccines to increase the humoral and/or cellular response to a delivered antigen. Combining the correct antigen and adjuvant can induce faster, more robust and more durable immune responses, and may also reduce the amount of antigen needed to induce protection. 

Since the 1990s, the use of lactic acid bacteria (LAB) as an oral vaccine platform has been explored against many pathogens and toxins. These vaccines have been shown to induce serum IgG and mucosal secretory (sIgA) as well as stimulate T cell responses.  

Most pathogens enter the body at mucosal sites. Defense of these barrier tissues is mediated by innate and adaptive immune responses, making mucosal vaccine delivery attractive due to the ease of administration and the common-mucosal immune system. Despite the benefits of mucosal vaccines, there are few available for use worldwide due to risk of reversion to virulence by the attenuated pathogen in the vaccine. If safety issues are ameliorated, the potential of LAB as mucosal vaccine vectors may be realized. A comprehensive chart from a 2019 review displays the probiotic and commensal bacteria that possess immunomodulatory/antiviral and vaccine adjuvant properties as shown in both animal and human research. 

 

Takeaway 

Researchers are racing to create vaccines to protect against the SARS-CoV-2 virus. There are likely to be many iterations and levels of effectiveness. The gut microbiota may influence vaccine response. Probiotics, by influencing the microbiota and immune response, may thereby impact vaccine response. In addition, probiotics such as LAB may act effectively as adjuvants. Studies should now focus on establishing optimal strains, doses and timing of administration in relation to vaccination. 

 

Clare Fleishman RDN, MS is a Registered Dietitian with the Academy of Nutrition and Dietetics and holds a master degree in nutrition science. She bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media and websites. From corporate whiteboards to refugee schools in Egypt, Fleishman agitates for personal and public change.  In 2010, she launched www.ProbioticsNow.com to share the cascade of new discovery in the microbiome. Always amazed at this “forgotten organ” Fleishman also creates white papers, blogs, videos and social media for the International Probiotics Association as well as continuing education platforms. 

 

References 

Ciabattini, Annalisa et al. “Role of the Microbiota in the Modulation of Vaccine Immune Responses.” Frontiers in microbiology vol. 10 1305. 3 Jul. 2019, doi:10.3389/fmicb.2019.01305 

Lynn, D.L. and Pulendran, B. “The potential of the microbiota to influence vaccine responses.” J Leukoc Biol vol. 103, 2 (2018):225-231. doi: 10.1189/jlb.5MR0617-216R 

Vilander, Allison C, and Gregg A Dean. “Adjuvant Strategies for Lactic Acid Bacterial Mucosal Vaccines.” Vaccines vol. 7,4 150. 16 Oct. 2019, doi:10.3390/vaccines7040150 

Vlasova, Anastasia N et al. “How the gut microbiome regulates host immune responses to viral vaccines.” Current opinion in virology vol. 37 (2019): 16-25. doi:10.1016/j.coviro.2019.05.001 

Zimmermann, Petra, and Nigel Curtis. “Factors That Influence the Immune Response to Vaccination.” Clinical microbiology reviews vol. 32,2 e00084-18. 13 Mar. 2019, doi:10.1128/CMR.00084-18 

Zimmermann, Petra, and Nigel Curtis. “The influence of the intestinal microbiome on vaccine responses.” Vaccine vol. 36,30 (2018): 4433-4439. doi:10.1016/j.vaccine.2018.04.066 

Zimmermann, Petra, and Nigel Curtis. “The influence of probiotics on vaccine responses - A systematic review.” Vaccine vol. 36,2 (2018): 207-213. doi:10.1016/j.vaccine.2017.08.069 

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