Adaptative immunity, COVID-19 reinfection and the microbiota
8 June 2020 – 4 min read
Now that the initial coronavirus expansion seems to be over and transmission rates are slowing down, public concern seems to be shifting to long-term issues, some related to immunity: Are those that have passed the SARS-CoV-2 virus protected from future re-infections? With vaccines still under development, is there any way coronavirus-specific adaptive immunity can be promoted today?
These questions seem to be key to predict how and when the world is going to recover from this pandemic. Unfortunately, clinical evidence is still not enough, and answers are changing and evolving constantly. In this article we will explain briefly what is known so far, and link it to our research field, the microbiota.
The first time a pathogen enters our body (like harmful bacteria that reach our blood stream through a wound) it encounters the main players of innate immunity, that will rapidly try to prevent the infection from spreading, generating an inflammatory response.
Depending on the type of infection and its magnitude, innate immunity might not be enough to control and eliminate the threat. In that situation, adaptive immunity, comprising B cells, T cells and immunoglobulins (or antibodies), plays a key role.
B cells and T cells will interact with specific molecules of pathogens (known as antigens) and will begin a slower but more effective response to fight back the infection. This response comprises the synthesis of specifically designed antibodies, that will guide the immune system to efficiently eliminate the concrete pathogen, allowing the body to regain a healthy state.
The great thing about acquired immunity is that, if the same pathogen re-enters the body, specific antibodies will be already available to fight back the infection faster and without complications.
The microbiota influences acquired immune responses in children and adults.
SARS-CoV-2 is quite a complex and sophisticated virus. Our immune system is able to identify it as a major threat and begin the response to eliminate it; however, it seems that the virus can block some of the signals secreted by our immune cells (called interferons) making the response less efficient and crippled1 In some people, even a limited immune response is enough to eliminate the virus, but in others this leads to a severe inflammation of the lungs, that can end in fatality.
Luckily, the defence mechanism of the virus is not enough to block one of the most important functions of adaptive immunity: the creation of selective antibodies. Studies have found high levels of antibodies to SARS-CoV-2 in recently recovered patients2.
After going through COVID-19 disease, the body will normally have virus-specific antibodies circulating in the bloodstream3. This could reduce the chances of a re-infection shortly after having been ill.
However, since the coronavirus SARS-CoV-2 has only been circulating in human hosts for six or seven months, there is no way to know how long this antibody-mediated adaptive immunity lasts. For now, scientists can only confirm an effective antibody response to the virus within two weeks after having overcome the disease. However, evidence from other viruses of the same family (other coronaviruses) is encouraging; research on SARS 1 and MERS suggests that some level of antibody-mediated immunity persists for at least two or three years, starting high and dwindling gradually as time goes by4-6.
For now, we will have to wait for new evidence to know exactly for how long we are immune to the virus after its infection. Thus, it is recommended to maintain protective measures in all cases, regardless of previous contact with the virus; the level of contagiousness of recovered COVID-19 patients is neither quite clear yet.
Great scientific advances are being made on the field of probiotics and immunity, including acquired immunity.
The immune system evolves from birth to old age, adapting and responding to the environment. Babies are born with immature immunity, which evolves and acquires memory while aging. As infants get older, their exposure to all kinds of antigens will help shape their immune response, in the short and long term. A healthy and well-adapted immune system is linked to a lower risk of infections, autoimmune diseases and even cancer7.
Interestingly, as already introduced in this article , the gut microbiota also plays an essential role in the development and maturation of our immune system. A diverse and rich microbiota will help develop adaptive immunity, ensuring a strong defence mechanism to infections and other threats8.
In the first stages of life, both gut microbiota and adaptive immunity development seem to be linked and intertwined. It has been observed that the microbiota has an impact on the formation of key components of the immune system9, including T-cells differentiation and B-cells maturation8.
In adults, a deficient communication between gut microbiota and immunity has been related to several diseases, including Crohn’s disease, ulcerative colitis and inflammatory bowel disease10-13. Even in auto-immune disorders and metabolic syndromes an altered gut microbiota has been observed14.
Some probiotics are able to directly influence some of the key players of immunity, through mechanisms not yet fully understood. More information in this article .
AB-IMMUNO strains (L. plantarum CECT 7315 and L. plantarum CECT 7316) were observed to induce the synthesis of IL-10 by immune cells in vitro15. Even more so, AB-DR7 strain (L. plantarum DR7) was able to increase IL-10 levels in a randomized clinical trial in humans, contributing to reduced frequency and symptoms of upper respiratory tract infections16.
IL-10 is a molecule with roles in both innate and adaptive immunity; it dampens excessive inflammation, and also modulates acquired immunity by promoting the proliferation of mature activated B cells17,18, thus facilitating the production of antibodies of types IgM, IgG, IgE and IgA 17,19,20.
Though more clinical evidence is needed to establish the full potential of some probiotic strains, we are beginning to see great advances on this field, both for adaptive and innate immunity.
1. Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, et al. Journal pre-proof Imbalanced host response to SARS-CoV-2 drives development of COVID-19. 2020; 2. Ni L, Ye F, Cheng M-L, Feng Y, Deng Y-Q, Zhao H, et al. Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals. Immunity. 2020 May 3 3. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Rydyznski Moderbacher C, et al. Journal Pre-proof Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. 2020. 4. Wu LP, Wang NC, Chang YH, Tian XY, Na DY, Zhang LY, et al. Duration of antibody responses after severe acute respiratory syndrome. Emerg Infect Dis. 2007;13(10):1562–4. 5. MO H, ZENG G, REN X, LI H, KE C, TAN Y, et al. Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significance. Respirology. 2006 Jan 1;11(1):49–53. 6. Payne DC, Iblan I, Rha B, Alqasrawi S, Haddadin A, Al Nsour M, et al. Persistence of antibodies against middle east respiratory syndrome coronavirus. Emerg Infect Dis. 2016 Oct 1;22(10):1824–6. 7. Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Vol. 282, Proceedings of the Royal Society B: Biological Sciences. Royal Society of London; 2015. 8. Zhao Q, Elson CO. Adaptive immune education by gut microbiota antigens. Vol. 154, Immunology. Blackwell Publishing Ltd; 2018. p. 28–37. 9. Eberl G, Lochner M. The development of intestinal lymphoid tissues at the interface of self and microbiota. Vol. 2, Mucosal Immunology. Mucosal Immunol; 2009. p. 478–85. 10. Stecher B. The Roles of Inflammation, Nutrient Availability and the Commensal Microbiota in Enteric Pathogen Infection. Microbiol Spectr. 2015 Jun 25;3(3). 11. Parlato M, Charbit‐Henrion F, Pan J, Romano C, Duclaux‐Loras R, Le Du M, et al. Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis . EMBO Mol Med. 2018 Apr;10(4). 12. Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, et al. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest. 2004 May 1;113(9):1296–306. 13. Macpherson A, Khoo UY, Forgacs I, Philpott-Howard J, Bjarnason I. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut. 1996;38(3):365–75. 14. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011 Mar 15;108(SUPPL. 1):4615–22. 15. Vilahur G, López-Bernal S, Camino S, Mendieta G, Padró T, Badimon L. Lactobacillus plantarum CECT 7315/7316 intake modulates the acute and chronic innate inflammatory response. Eur J Nutr. 2015 Oct 26;54(7):1161–71. 16. Chong H-X, Yusoff NAA, Hor Y-Y, et al. Lactobacillus plantarum DR7 improved upper respiratory tract infections via enhancing immune and inflammatory parameters: A randomized, double-blind, placebo-controlled study. J Dairy Sci. 2019;102(6):4783–97. 17. Rousset F, Garcia E, Defrance T, Peronne C, Hsu D-H, Kastelein R, Moore KW, Banchereau J. IL-10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc. Natl. Acad. 1992. Sci. USA 89:1890–93. 18. Moore KW, R de Waal Malefyt, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 Receptor. Annu Rev Immunol. 2001;19:683-765. 19. Nonoyama S, Hollenbaugh D, Aruffo A, Ledbetter JA, Ochs HD. B cell activation via CD40 is required for specific antibody production by antigen-stimulated human B cells. J. Exp. Med. 1993;178:1097–1102. 20. Wang J, Ma L, Yang S, Wang S, Wei X, Song S. IL-10-Expressing Th2 Cells Contribute to the Elevated Antibody Production in Rheumatoid Arthritis. Inflammation. 2016 Jun;39(3):1017-24.