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Introduction to the clinical stations
Published in Sukhpreet Singh Dubb, Core Surgical Training Interviews, 2020
Central to the diagnosis is the combination of cystoscopy and urine cytology. Low grade tumours are easy to visualise but often have negative cytology. In contrast to this, higher-grade tumours can be more difficult to see due to their flattened appearance, however, they more often appear positive in urinary cytology. Treatment centres around the degree of invasion. In a pathology that spares the detrusor muscle, transurethral resection is the management of choice; although effective, there is a high rate of recurrence. Intravesical chemotherapy is employed in order to reduce the distribution of malignant cells or ‘seeding’. In higher grade, more aggressive tumours that have not crossed the detrusor muscle, immunotherapy – using the tuberculosis vaccine BCG – is used with close follow-up. In patients who have muscle-invasive tumours, neoadjuvant chemotherapy, cystoprostatectomy and the surrounding pelvic lymph nodes undergo lymphadenectomy.
The Defended Body
Published in Roger Cooter, John Pickstone, Medicine in the Twentieth Century, 2020
The first modern vaccines tried on a large scale were for typhoid, in the British and the French armies during World War I. Although slower than suggested by the triumphalist announcements of pioneering microbiologists, the quest for further vaccines succeeded for tetanus (1921), diphtheria (1923), yellow fever (1932), and then after World War II, for poliomyelitis, measles, whooping cough, and hepatitis. Most of these vaccines were widely accepted and some were made compulsory at the eve of World War II, with one notorious exception — BCG. This long-awaited tuberculosis vaccine, launched in France in 1921 by Pastorians Albert Calmette and Camille Guérin, was widely tried in French colonies and made compulsory in metropolitan France in 1938, but it remained controversial and never gained the international acceptance of its predecessors.
Medical microbiology
Published in Lois N. Magner, Oliver J. Kim, A History of Medicine, 2017
When marked variations in the virulence of different strains of the tubercle bacillus were discovered, scientists hoped that a particular strain could play the role cowpox served in preventing smallpox. But evaluating tuberculosis vaccines is very difficult; in some areas, almost everyone has been exposed to the bacillus and many have long-standing but dormant infections. Nevertheless, a widely used vaccine derived from a live, attenuated strain was developed by Albert Léon Charles Calmette and Camille Guérin. Since the 1920s BCG (Bacille Calmette-Guérin) has been used as a vaccine against tuberculosis despite questions about its safety and efficacy. Indeed, the disaster that occurred in Lübeck, Germany, in 1930 created widespread fear of the vaccine. More than 200 of the infants vaccinated with BCG contracted tuberculosis and 72 of these babies died. Investigators later found that the nonvirulent BCG culture had been contaminated by a dangerous strain that was being used in the same laboratory.
GMMA as a ‘plug and play’ technology to tackle infectious disease to improve global health: context and perspectives for the future
Published in Expert Review of Vaccines, 2022
Diego Piccioli, Erika Bartolini, Francesca Micoli
Unfortunately, vaccines are not available against several pathogens responsible for serious diseases in low and middle-income countries, such as AIDS, Shigellosis, invasive non-typhoidal Salmonella (iNTS), ETEC [67,69–73]. In the case of Malaria, a vaccine that is able to reduce the disease in young children has been developed [74]. This vaccine demonstrated a 30% efficacy in Phase III trial and a Malaria Vaccine Implementation Programme was established to support the introduction of the vaccine through the routine immunization programs in selected areas of Africa, with the aim to evaluate the vaccine’s public health impact on a broader scale [74] (https://www.who.int/news-room/fact-sheets/detail/malaria). Tuberculosis has a vaccine (BCG; first used in 1920) currently available, but does not prevent primary infection and reactivation of latent pulmonary infection, thus its impact on the decline of disease incidence is limited [66,75]. Recently, a Tuberculosis vaccine candidate showed 54% of protective efficacy against the disease over 2 years of follow-up in a Phase IIb trial among Human Immunodeficiency Virus (HIV)-negative adults with evidence of latent Tuberculosis infection [75].
Exploit T cell Immunity for Rapid, Safe and Effective COVID-19 Vaccines
Published in Expert Review of Vaccines, 2020
Leonard Moise, Ted M. Ross, Daniel F. Hoft, William D. Martin, Anne S. De Groot
Some may question the feasibility of a T cell-directed vaccine strategy. Apart from the tuberculosis vaccine Bacille Calmette–Guérin (BCG), no vaccine that relies primarily on a T cell response to protect has been licensed. ‘But it was never done!’ did not stop scientists in wartime from achieving epic goals once thought improbable. Urgent necessity has always been known to accelerate scientific development. We are fighting a war against SARS-CoV-2 and we suggest that this is an opportunity to mobilize against COVID-19 with a vision that capitalizes on our collective knowledge, skills, and ingenuity. Alongside antibody generating vaccines, T cell-directed vaccines should be pursued, in similar formulation and delivery platforms that are currently under study with spike glycoprotein, including nucleic acid, protein, and vectored formats. If we develop T cell-directed vaccines with the same vigor that is being devoted to spike glycoprotein, we are more likely to succeed in the battle against SARS-CoV-2 and may even develop vaccines that are ready to protect future generations against other pathogenic novel coronaviruses as they are certain to emerge and threaten humanity in the future.
Selection of adjuvants for vaccines targeting specific pathogens
Published in Expert Review of Vaccines, 2019
Indranil Sarkar, Ravendra Garg, Sylvia van Drunen Littel-van den Hurk
Mechanisms of antibody-mediated protection against TB include opsonization, complement activation, and Fc receptor engagement. Current research is focused on adjuvants that act on innate lymphoid cells (ILCs), NK cells and non-classical T cells such as CD1, MR1, HLA-E and γδ T cells present in large numbers in the circulation and mucosa [98]. Although the immune correlates of protection from TB disease are not validated yet, vaccines currently in clinical development predominantly focus on generating CD4+ and CD8+ Th1-type immune responses. Adjuvants such as mineral salts, saponin, Emulsigen®, micro- or nanoparticles, toxin derivatives, cationic lipids, CpG DNA, adjuvant systems and cytokines have been tested in subunit vaccine preparations, either alone or in combination with BCG in a prime-boost strategy [97]. The strongest Th1-inducing adjuvants for TB are unmethylated mycobacterial DNA and CpG ODN, which promote CTL activation and IFN-γ production [97]. TLR2/1 and TLR2/6 ligands are presented on the surface of Mtb (triacylated and diacylated forms of mycobacterial p19 lipoprotein) or secreted by the bacterium, while NLRs such as NOD2 are responsible for intracellular recognition of mycobacteria [99]. Novel adjuvants, including DDA, TDB, IC31, poly(I:C), gelatin, CpG ODN, MPLA, glycopyranosyl lipid adjuvant (GLA) in combination with squalene (SE) known as GLA-SE, MF59, CAF01, and AS01B are also being clinically tested. DDA promotes generating humoral, cell-mediated and IFN-γ responses against Mtb, while AS01 and MF59 induce strong Th1 immunity against Mtb. All these adjuvanted subunit vaccines induce protective immunity and enhance BCG-primed immunity in animal models [100]. In a randomized, double-blind, phase 2b trial, a candidate tuberculosis vaccine, M72/AS01E, demonstrated a clinically acceptable safety profile and conferred 54% protection against active pulmonary tuberculosis in adults with latent Mtb infection [101]. Nanoparticle-based vaccines are critical for the induction of protective Th1-type immune responses to intracellular pathogens. The liposomal CAF01 adjuvant promoted Th1 and long-lasting memory T cell response in human TB vaccination trials. CAF01-adjuvanted TB vaccine stimulates the CLR, and Mincle, and triggers the Syk/Card9 signaling cascade to activate the Th17 signaling pathway [48].