Antigenic escape

The most common of antigenic escape mechanisms, homologous recombination, can be seen in a wide variety of bacterial pathogens, including Helicobacter pylori, a bacterium that infects the human stomach. While a host's homologous recombination can act as a defense mechanisms for fixing DNA double stranded breaks (DSBs), it can also create changes in antigenic DNA that can create new, unrecognizable proteins that allow the antigen to escape recognition by the host's immune response. Through the recombination of H. pylori's outer membrane proteins, immunoglobulins can no longer recognize these new structures and, therefore, cannot attack the antigen as part of the normal immune response.[2]

African trypanosomes are parasites that are able to escape the immune responses of its host animal through a range of mechanisms. Its most prevalent mechanism is its ability to evade recognition by antibodies through antigenic variation. This is achieved through the switching of its variant surface glycoprotein or VSG, a substance that coats the entire antigen. When this coat is recognized by an antibody, the parasite can be cleared. However, variation of this coat can lead to antibodies being unable to recognize and clear the antigen. In addition to this, the VSG coat is able to clear the antibodies themselves to escape their clearing function.

Trypanosomes are also able to achieve evasion through the mediation of the host's immune response. Through the conversion of ATP to cAMP by the enzyme adenylate cyclase, the production of TNF-α, a signaling cytokine important for inducing inflammation, is inhibited in liver myeloid cells. In addition, trypanosomes are able to weaken the immune system by inducing B cell apoptosis (cell death) and the degradation of B cell lymphopoiesis. They are also able to induce suppressor molecules that can inhibit T cell reproduction.[3]

Many head and neck cancers are able to escape immune responses in a variety of ways. One such example is through the production of pro-inflammatory and immunosuppressive cytokines. This can be achieved when the tumor recruits immunosuppressive cell subsets into the tumor's environment. Such cells include pro-tumor M2 macrophages, myeloid-derived suppressor cells (MDSCs), Th-2 polarized CD4 T-lymphocytes, and regulatory T-lymphocytes. These cells can then limit the responses of T cells through the production of cytokines and by releasing immune-modulating enzymes.[1] Additionally tumors can escape antigen-directed therapies by loss or down-regulation of the associated antigens, as well demonstrated after checkpoint blockade immunotherapy[6] and CAR-T cell therapy[7] though more recent data indicate that this may be prevented by localized bystander killing mediated by fasL/fas.[8] Alternatively therapies can be developed to encompass multiple antigens in parallel.[9]

While vaccines are created to strengthen the immune response to pathogens, in many cases these vaccines are not able to cover the wide variety of strains a pathogen may have. Instead they may only protect against one or two strains, leading to the escape of strains not covered by the vaccine.[5] This results in the pathogens being able to attack targets of the immune system different than those intended to be targeted by the vaccination.[4] This parasitic antigen diversity is particularly troublesome for the development of the malaria vaccines.[5]

In order to fix this problem, vaccines must be able to cover the wide variety of strains within a bacterial population. In recent research of Neisseria meningitidis, the possibility of such broad coverage may be achieved through the combination of multi-component polysaccharide conjugate vaccines. However, in order to further improve upon broadening the scope of vaccinations, epidemiological surveillance must be conducted to better detect the variation of escape mutants and their spread.[4]