unlikely that vaccination against a second will be effective. This implies that balanced responses against all four virus serotypes must be established with the first vaccine dose. Activation of naive B cells that recognize novel epitopes may be attenuated with repeated infection with variant influenza viruses. However, the impact of antigenic sin on protection has not been well established and appears to differ with each infectious agent vaccine, geographic location, and age. Research done in 2011 found reduced antibody responses to the 2009 pandemic H1N1 influenza vaccine in individuals who had been vaccinated against the seasonal A/Brisbane/59/2007 (H1N1) within the previous three months. The relative ineffectiveness of the bivalent booster against the SARS-CoV-2 Omicron variant in patients who had previously received COVID-19 vaccines has been attributed to immunological imprinting. In cytotoxic T cells A similar phenomenon has been described in cytotoxic T cells (CTL). It has been demonstrated that during a second infection by a different strain of dengue virus, the CTLs prefer to release cytokines instead of causing cell lysis. As a result, the production of these cytokines is thought to increase vascular permeability and exacerbate damage to endothelial cells, resulting in dengue hemorrhagic fever. Several groups have attempted to design vaccines for HIV and hepatitis C based on induction of CTL response. The finding that the CTL response may be biased by original antigenic sin may help to explain the limited effectiveness of these vaccines. Viruses like HIV are highly variable and undergo mutation frequently; due to original antigenic sin, HIV infection induced by viruses that express slightly different epitopes (than those in a viral vaccine) might fail to be controlled by the vaccine. It has been hypothesized that: if original antigenic sin is a common phenomenon, a naively designed single-component vaccine could conceivably make an infection even worse than if no vaccination at all had occurred. The hypothesized mechanism is that the immune response would be "trapped" in a less effective response. Therefore a recommendation was made for vaccines with multiple components or that target conserved epitopes. See also Antibody-dependent enhancement Cell mediated immunity Genomic imprinting Humoral immunity Polyclonal response Local optimum References Virology Immunology