Immune memory: A perspective to SARS-CoV-2 vaccination21 July 2020
Vaccination is based on the concept of immune memory. It is one of the key features of the adaptive immune system upon infection. Currently, many vaccines are evaluated by the magnitude of antigen-specific antibody titers in serum or mucosa after vaccination. The antibody-mediated humoral immune memory is established regardless of the magnitude and duration of immune reactions, thus assessment of vaccine efficacy should be performed for several years after vaccination, which is disadvantageous for prevalent and pandemic infections, especially those are highly variable and/or cause persistent and latent infections (e.g., human immunodeficiency viruses, hepatitis C virus, Mycobacterium tuberculosis). It is also proven difficult to develop successful vaccines against acute infections (e.g., respiratory syncytial virus, malaria) where the natural infection itself does not result in complete protection against re-infection. Now, the final question is do the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines going to suffer these problems or not! In fact, this virus is also found variable, several mutations have been reported within a short time, causing persistent and latent infections. Moreover, re-infection and the short term antibody response has been also reported in this case. A new issue arose in the case of SARS-CoV-2 infection against host antibody levels, where it has been reported that the patient serum was negative for the antibodies IgG and IgM within 3 months against the virus. Even, the patient did not have viral S1 specific B cells. However, in this case the responses of the memory cells (e.g., B cells, T cells, natural killer cells) upon re-infection with the virus yet to be investigated.
During the secondary immune response, all the memory cells are involved in the reaction against foreign antigens, including pathogens, and take part in autoimmune diseases, but also are crucial to immunological tolerance and vaccine therapy. Future advances in comprehending immunological memory require answers to several questions including- the identity of the genetic and molecular components required for the maintenance of immunologic memory, the differences of memory responses of various populations of lymphocytes involved in the adaptive immune response, recognition mechanism of diverse self-antigens, genetic interference for the antigen/microorganism identification by the memory cells, and methods for enhancing/suppressing the memory response in a variety of clinical situations. To be noted that age, sex, antigen quality and loads (including host antigens), maintenance and preservation of memory cells' integrity, genetic and epigenetic factors, and pathogen associated and danger associated molecular patterns also affects the functions of immune memory cells.
Generally, the long-lived memory plasma cells (B memory cells) and memory helper T cells that contribute to humoral immune memory are generated in the bone marrow after migration of memory cell precursors through the bloodstream. Therefore, it should be a novel evaluation strategy to assess the precursors of memory cells in the blood in the early phase of the immune reaction(s). Recent evaluation systems for vaccines point toward the measurement of memory cell quality with regards to cytokine secretion as a protective correlate in addition to antibody titers in serum during the course of an immune response. Even though the generation of immune memory provides the basis for the concept of vaccination, direct assessment of immune memory cells and their precursors has not yet been established as a correlate of protection.
In general, the immune memory is characterized by the ability of the immune system to constantly provide antibodies, and also responds more rapidly and effectively to pathogens that have been encountered previously. After clearance of pathogens, the generated memory plasma cells, continuously provide pathogen-specific antibodies for protection up to a lifetime. When the immune system is re-challenged with the same pathogen, memory T helper (Th) cells and memory B cells that have been generated in the course of the primary immune response, elicit a more rapid recall response at stronger magnitude than naive cells do. Thus, the protective immunity is accomplished in a consequence of immune memory, i.e. by the persistence of memory cells.
During an immune response, some antigen-specific activated B cells differentiate into memory B cells and short-lived plasma cells. Upon a recall response, memory B cells differentiate into plasma blasts, migrate from the spleen into the bone marrow (BM) in a CXCR4-CXCL12 and S1P1-S1P dependent manner and eventually become memory plasma cells. The chemokine CXCL12 guides the migration of memory plasma cell precursors to their niches comprised of reticular VCAM-1+ stromal cells. On the other hand, the prominent plasma cell survival factors, interleukin (IL)-6 and a proliferation inducing ligand (APRIL), secreted by megakaryocytes and eosinophils in the direct vicinity of VCAM-1+ CXCL12+ stromal cells, provides an optimized environment to maintain the survival niche for memory plasma cells in the BM. They secrete several thousand antibodies per second for years, although they are resting in terms of proliferation. Within the BM, these plasma cells are maintained in the absence of antigen, but rely on factors such as CXCL12, integrin alpha4, APRIL and IL-6 provided by stromal cells, megakaryocytes and eosinophils. However, the memory B cells also reside in the spleen.
Therefore, the quantification of memory cell precursors in the blood, for example, CD49b+T-bet+ resting memory Th cell precursors and CXCR4+ S1P1+ memory plasma cell precursors, can be advantageous in order to determine the quality of protection upon the prospective establishment of humoral immune memory, since immune memory in the BM can be established regardless of the magnitude of the immune reaction. Additionally, memory precursor cells are detectable in peripheral blood within one week after vaccination, which offers an enormous time saving in comparison to the detection of neutralizing antibodies or antigen-specific memory cells that appear at much later time points of the immune reaction.
(Dr. Muhammad Torequl Islam is Assistant Professor, Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University. E-mail: [email protected])