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An Introduction to the Immune System and Vaccines
Published in Patricia G. Melloy, Viruses and Society, 2023
The term “antigenic drift” is used to describe changes in the shape of these key antigen proteins of the virus as the strain evolves, and “antigenic shift” refers specifically to changes in these antigens through the combination of new nucleic acid segments, such as what occurs with the influenza virus (Minkoff and Baker 2004b). One could say these changes to viral surface antigens are analogous to a wanted criminal putting on a new disguise to avoid capture by the police. In a similar analogy, Professor Sunetra Gupta described a pathogen as slightly changing its wardrobe over time to avoid detection, in a series of cartoons presented as a part of her Royal Society lecture in 2009 (Society 2009). Finally, insidiously, some viruses like Epstein-Barr virus and herpes simplex virus can affect the function of immune cells and their proteins, cutting the immune system off at its knees (Coico and Sunshine 2015).
Routine maternal immunizations for all pregnant women
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
While antigenic drift describes minor genetic changes in the viral genome, “antigenic shift” refers to major genetic alteration. The major pandemic strain in 1917 to 1918 was caused by an H1N1 subtype influenza A virus and this presented until 1957 when the H2N2 subtype appeared. The H2N2 subtype underwent a major antigen shift in 1968 resulting in the H3N2, which has been circulating until the present time. An H1N1 subtype emerged in 1977 and has been co-circulating with the H3N2 subtype. Current influenza vaccine contains one H3N2 strain, one H1N1 strain, and one influenza B strain. In March 2009, a novel H1N1 subtype emerged in Mexico and is the result of influenza A strains from pigs, birds, and humans. Recombinant analysis showed triple-reassessment swine H1N1 influenza virus coming from classic swine, North American lineage; avian, North American lineage; human (seasonal) H3N2 and human seasonal (H1N1) strain initiated a worldwide pandemic (7).
Antiviral Agents and Rational Drug Design
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The glycoproteins NA and HA are present on the outer surface of the virion, so can serve as antigens; potentially recognised by antibodies and the cells of the immune system. While the amino acids in the active site of NA and HA are highly conserved, the influenza virus is adept at varying the amino acid sequence elsewhere in the proteins: this propensity for mutation hinders recognition by the immune system and limits the ability to develop vaccines with these antigens. The reason for this high level of antigenic variation is because the RNA polymerase enzyme is highly error prone. This results in the production of RNA that codes for NA and HA being inconsistent. Variation in the RNA code means that different sequences of amino acids give different antigenic variants, resulting in different strains of flu. Where the variation is small, it is referred to as antigenic drift. When there is large variation, called antigenic shift, this can lead to more serious epidemics and pandemics.
Yin and yang of immunological memory in controlling infections: Overriding self defence mechanisms
Published in International Reviews of Immunology, 2022
Roshan Kumar Roy, Rakhi Yadav, Aklank Jain, Vishwas Tripathi, Manju Jain, Sandhya Singh, Hridayesh Prakash
Developing a specific type of vaccine is challenging due to various limitations, for Instance, live attenuated vaccines although develop strong cellular and antibody response but they might undergo secondary mutations leading to reversal of virulence. In comparison to them, heat killed vaccines ensure more safety but they induce weaker immune response. On the other hand, the application of toxoid vaccines is limited only to bacterial infections [105]. Further, for pathogens that replicate fast, the effector memory pool acts as a Frontline as they can be reactivated fast. For such organisms, high avidity T cells are important whereas for organisms that are slow growing, both high and low avidity T-cells are sufficient. Thus, during vaccine development pathogen’s diversity and evolution are also important to be considered, as evolution can lead to antigenic shift hampering the efficacy of vaccine [106].
Better, Faster, Stronger: mRNA Vaccines Show Promise for Influenza Vaccination in Older Adults
Published in Immunological Investigations, 2021
Jenna M. Bartley, Andreia N. Cadar, Dominique E. Martin
Along with the increased efficacy in older adults, the markedly shorter timeline for the production of mRNA vaccines makes them a particularly attractive alternative to seasonal influenza vaccines. As illustrated in Figure 1, the mRNA vaccine platform would allow vaccine production to be completed in only 2–3 months, compared to 6–8 months using egg-based methods. This would allow WHO strain recommendations to occur much closer to when seasonal vaccination occurs, reducing the likelihood for vaccine and circulating strain mismatch. Additionally, mRNA platforms would not have the potential to have egg-adaptive mutations during propagation. Importantly, the shorter timeline for vaccine production would also allow for quick recreation of influenza vaccines. This would be incredibly advantageous when circulating strains have dramatic antigen drifts in short periods of time or if pandemic strains emerge due to antigenic shift. The ability to have highly controlled production that is rapid and scalable would be immensely valuable for influenza vaccines.
Modeling human pediatric and adult gliomas in immunocompetent mice through costimulatory blockade
Published in OncoImmunology, 2020
Xiaoyan Lan, Dorota A. Kedziorek, Chengyan Chu, Anna Jablonska, Shen Li, Mihoko Kai, Yajie Liang, Miroslaw Janowski, Piotr Walczak
In this study, we showed that costimulation blockade (CTLA-4-Ig and MR1) in immunocompetent mice resulted in long-term different glioma xenografts (human GBM1, GBM551, and DIPG) survival. These results align well with the previous reports on the prevention of rejection of organs25,51-53 or stem cell26 transplantation. All of the animals in GBM1 and DIPG groups, together with three of five animals in GBM551 group treated with both agents, experienced extended (up to 182 d) rejection-free allograft survival. However, two animals in GBM551 group treated with this costimulation inhibitor experienced late, biopsy-proven rejection. Given that the half-life of CTLA-4-Ig is 90 hours and MR1 is 12 d in mouse blood serum,54,55 we speculate that the GBM551 tumor regression may have been triggered in several mechanisms. One possibility is inflammatory/infectious insult triggering leukocyte infiltration and enhancing immune response, as our immunofluorescence results showed substantial leukocyte (CD45) and T-cell (CD3) infiltration and microglial (Iba1) activation in the tumor. Besides, we noticed the disruption of BBB in the immunocompetent mice of GBM551 tumor, which might also contribute to the tumor regression, as peripheral adaptive and innate immune cells, including monocytes, neutrophils, T cells, and B cells, can enter the brain parenchyma and execute distinct cell-mediated effects when the BBB is impaired.56 Finally, it is possible that over the period of several months, new mutations within the tumor cells caused antigenic shift and recognition by immune system.