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Immunization
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael F. Para, Susan L. Koletar, Carter L. Diggs
In addition to the antigenic components to be described below, vaccine preparations usually contain other constituents, some active and some inert. Among the most important are adjuvants, i.e., agents which increase immunogenicity. Adjuvants are proving to be especially important in recombinant subunit vaccines which as a group tend to be poorly immunogenic. It is now appreciated that bacterial whole cell vaccines may owe at least a portion of their immunogenicity to naturally occurring materials such as lipid A which act as natural adjuvants. Their particuiate nature may aiso be a contributing factor, since the immune system processes particulate and soluble antigens differently. Currently, the only adjuvant licensed in the United States is alum. Alum consists of either aluminum hydroxide or aluminum phosphate and is an insoluble substance with the property of adsorbing protein to its exposed surfaces. The efficacy of alum in promoting the immune response is poorly understood, but may be related to the concentration on the particles of alum of many molecules of antigen, thus presenting to the immune system particles covered with multiple epitopes. As occurs with cellular vaccines, so with alum-containing vaccines, the persistence of antigen at the injection site due to the decreased solubility of the complex may also play a role in increasing immunogenicity.
BCG and Other Vaccines
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Live attenuated whole-cell vaccines have the potential advantages over protein-adjuvant and viral-vectored subunit vaccines of a comprehensive antigen repertoire and greater similarity to natural infection. Such BCG replacements aim to improve on both efficacy (particularly in the developing world) and safety, permitting use in infants with HIV infection. Any BCG replacement must demonstrate non-inferiority to BCG in protection against other mycobacterial infections such as leprosy, and potential non-specific effects in reducing all-cause mortality in infants, as well as efficacy against severe forms of TB and pulmonary disease.
Native And Acquired Resistance To Infection With Cryptococcus Neoformans
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
These observations were essentially confirmed 3 years later by Abrahams and Gilleran,94 who pointed out the critical dosage necessary for maximal protection. Excess whole-cell vaccine,94 as was the case with excess polysaccharide, resulted in diminished protection. Ability to survive was equated with decreased multiplication of cryptococci in the organs of vaccinated mice.
On the continuous (R)evolution of antibody-based and CAR T cell therapies in multiple myeloma: an early 2022 glance into the future
Published in Expert Opinion on Pharmacotherapy, 2022
Vincent Sunder-Plassmann, Osman Aksoy, Judith Lind, Martin Pecherstorfer, Sonia Vallet, Klaus Podar
Excitingly, in addition to naked mAbs, CARs, and BsAbs, several innovative therapeutic vaccine approaches are on the horizon. For example, preclinical data highlight the anti-MM activity of trispecific Abs (TsAbs) as a further development of Ab- based therapies. Indeed, SAR442257, a TsAb directed against CD3, the co-stimulatory T cell receptor CD28, and CD38 demonstrated an in vitro killing potency against MM 3-to-4-log higher than the CD38mAb daratumumab [127]. Moreover, non-cellular, multiepitope vaccine approaches include the utilization of antigen-specific peptides; whole-cell vaccine approaches include the employment of whole cell dendritic cell/tumor cell fusion, tumor-derived apoptotic bodies, and tumor lysates. Ongoing trials investigate whether their use translates into delayed progression (i.e. of smoldering MM) or elimination of minimal residual disease [128].
The development of ghost vaccines trials
Published in Expert Review of Vaccines, 2020
Killed whole-cell vaccines are the first-generation form of immunoprophylactic preparations that protected the human-race from several epidemic outbreaks. Inactivation of microbes usually depends on chemical or physical means that kill the viable cells or permanently denature their genetic content [1]. Although inactivated vaccines are easy to produce and safe, they have several drawbacks [2]. Unlike attenuation, the inactivation process may alter the 3-dimensional structure of the antigenic determinants or even fractionates the microbial cells; hence, either it reduces or sometimes increases their immunogenicity. Inactivation procedures provide doubtful complete killing, which may propose a high risk for blood-borne pathogens [2-4]. Although killed vaccines induce a predominantly T-cell dependent humoral immune response, their multi-antigenic structure is thought to induce an immunological noise to the immune system or can cross-react with the beneficial and the self-antigens [5-7]. Despite those defects, inactivated vaccines owe a higher safety over the live-attenuated ones.
Trends and costs of pertussis hospitalizations in Portugal, 2000 to 2015: from 0 to 95 years old
Published in Infectious Diseases, 2018
Sara Melo Oliveira, Manuel Gonçalves-Pinho, Alberto Freitas, Hercília Guimarães, Inês Azevedo
The introduction of the whole-cell vaccine resulted in a significant decrease of the global incidence of pertussis [5,6]. However, pertussis remains an endemic disease with frequent outbreaks, and an important cause of morbidity and mortality, even in countries with high vaccination coverage [7]. Most deaths and hospitalizations occur during the first weeks or months of life [8]. Although 63,000 deaths due to pertussis were estimated in children aged less than 5 years by the World Health Organization (WHO) in 2013, a shift in the age distribution of pertussis towards older age groups (adolescents and young adults) has also been recently reported, particularly in some high income countries, where acellular vaccines have replaced whole-cell vaccines for primary vaccination series [6]. However, this age shift had already been noticed even before the introduction of acellular vaccines, in the United States [9] and in Europe [10,11]. Waning vaccine-induced immunity in adolescents and adults after vaccination with acellular or whole-cell vaccines, and the lack of natural or vaccine boosters were addressed as the main reasons for the recent resurgence of pertussis. Active surveillance [11], genetic changes in circulating B. pertussis strains, increased sensitivity of diagnostic tests [12], vaccine hesitancy [13] or non-compliance with the recommended vaccination schedule [14] are additional contributory factors to the resurgence of pertussis.