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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Schistosomiasis again provides a good example. The most severe manifestations are observed only in those patients who are heavily infected with many worms. Light infections tend to be asymptomatic. Thus, an anti-schistosome vaccine would be useful even if it does not result in sterilizing immunity. Furthermore, when infected individuals are chemotherapeutically cured, resistance to reinfection is eventually observed in at least some individuals, suggesting that vaccination may be a feasible option. Attenuated schistosome larval stages have been used to establish resistance in certain animals such as rhesus monkeys, which are subsequently rendered resistant to infection, suggesting that at least in these non-human primates there is an immunological mechanism at work that prevents infection. If this mechanism can be elucidated, then it may be possible to invoke a similar process in humans via vaccination. And there is no shortage of candidate antigens to be used in a subunit, anti-schistosome vaccine, although few have reached even preliminary clinical trials. One such antigen is glutathione-S-transferase, a group of enzymes involved in the detoxification of various compounds. In primate models, subunit vaccines containing this antigen from some forms of the enzyme result in a significant reduction in adult worm numbers and egg production. The reduction in eggs is particularly noteworthy because so much of the pathology seen in schistosomiasis results from the host response to eggs lodged in various tissues.
The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
Schistosomiasis provides a good example. The most severe manifestations are observed only in those patients who are heavily infected with many worms. Light infections tend to be asymptomatic. Thus, an anti-schistosome vaccine may be useful even if it does not result in sterilizing immunity. Furthermore, when infected individuals are chemotherapeutically cured, resistance to reinfection is eventually observed in at least some individuals, suggesting that vaccination may be a feasible option.
Host-Directed and Immune-Based Therapies for Human Immunodeficiency Virus Infection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Hernan Valdez, Michael M. Lederman, Bharat Ramratnam, Timothy P. Flanigan
In challenge studies, initial studies in 1990 showed that immunization with attenuated SIV did not prevent infection but did prevent early disease in rhesus macaques. Later studies by the same group [125] showed that three strains of SIV, attenuated via recombination, induced a spectrum of anti-SIV immunity that was inversely associated with the degree of attenuation and that only the least attenuated virus-induced resistance to challenge infection. Numerous studies have also been performed with nef-deleted SIV to induce attenuation. Initial studies showed the protective effects of a live attenuated SIV vaccine with deletion in the nef gene [122]. Recent work [117] provides additional information regarding the vaccine potential of gene-deleted virus. This study showed that by using a triply deleted SIV (lacking nef, vpr, and upstream U3) protection could be achieved and increased with the length of vaccination time. This protection was attained without the generation of complete sterilizing immunity to the challenge infection. The data from these studies have indicated that attenuated viruses may fall into two classes: attenuated viruses with regard to replicative ability and attenuated viruses that, regardless of their ability to replicate, do not produce disease. The observation of vaccine protection to challenge infection by attenuated SIV has spurred interest in this vaccine approach. Enthusiasm has to be tempered, however, since numerous safety issues, such as oncogenesis, genetic instability, vertical transmission, and viral persistence and protection for de novo generated viral variants, remain to be addressed. In addition, studies using nef-deleted HIV isolates have initially failed to induce protection to a challenge HIV infection in chimpanzees.
Looking to the future: is a universal coronavirus vaccine feasible?
Published in Expert Review of Vaccines, 2022
Vipin M. Vashishtha, Puneet Kumar
Current SARS-CoV-2 vaccines have certain limitations. They are highly effective against severe disease, hospitalization and death, however, their ability against infection and transmission of the SARS-CoV-2 virus is limited, particularly against the more infectious delta variant. Hence, they are not able to provide sterilizing immunity. The challenge posed by the emergence of new variants and waning of immunity of current Covid-19 vaccines is huge. We are fiercely engaged in a race with the virus. Two large epidemics related to CoVs early in this century followed by this ongoing COVID-19 pandemic has demonstrated clearly how these zoonoses can disrupt our lives. And in all probability, the COVID-19 pandemic would not be the last one. We need to be better prepared for future pandemic threats. The development of hundreds of vaccine candidates and roll out of tens of them within a year of isolation of the virus has also aptly shown what a global will and pro-activeness can deliver. Proof of concept has been demonstrated by the above-cited studies.
Chlamydia trachomatis vaccines for genital infections: where are we and how far is there to go?
Published in Expert Review of Vaccines, 2021
Luis M. de la Maza, Toni L Darville, Sukumar Pal
The main goal of a C. trachomatis vaccine should be to elicit protection against long-term sequelae in females, e.g. PID, chronic pelvic pain, ectopic pregnancy and infertility. The possibility that a vaccine will induce ‘sterilizing immunity’ is highly unlikely since few vaccines, if any, elicits this type of protection [183]. The successful completion, of a Phase 1 clinical trial of a C. trachomatis vaccine, marks a turning point in a long road to control the pandemic caused by this pathogen [110]. This vaccine formulation, tested in three separate animal models, elicited protection against vaginal shedding but there is no experimental data supporting that it protects against long-term sequelae. The expectation that a decrease in vaginal shedding will correlate with protection in the upper genital tract is reasonable but not proven. This type of vaccine will likely decrease transmission. That, by itself, will have a major impact on the number of new genital infections and long-term sequelae.
Understanding host immune responses to pneumococcal proteins in the upper respiratory tract to develop serotype-independent pneumococcal vaccines
Published in Expert Review of Vaccines, 2020
Theano Lagousi, Paraskevi Basdeki, Marien I De Jonge, Vana Spoulou
More importantly, considering that some protein antigens are common among different serotypes, such vaccines have the potential to offer serotype-independent protection against NP colonization and subsequent disease [13]. Targeting conserved proteins would theoretically have the potential to induce broad protection and prevent serotype replacement. Indeed, none of the protein antigens studied so far is able to interrupt pneumococcal carriage when used as a single vaccine antigen. This lack of sterilizing immunity may also allow natural booster responses, due to low-grade circulation, which will indirectly contribute to the protective efficacy. Moreover, as most protein antigens have several allelic variants among different serotypes, there are strains that share the same variant, while cross-reactions among different variants have also been described [19]. Using distinct immunodominant epitopes within pneumococcal proteins that are highly conserved among the majority of serotypes will further expand the induction of serotype-independent protection against pneumococcal carriage and disease [14]. Besides, the combination of different protein antigens would ideally offer a robust and long-lasting immune response that remains localized to the nasopharynx (mucosal immunity) and has the potential to protect against pneumococcal disease, while controlling, but not disrupting pneumococcal colonization. Nevertheless, even such changes may alter the overall microbiome balance at the mucosal site of the nasopharynx, and the possibility of the emergence of new pathogens, even if assumed to be slight, cannot be excluded. Therefore, continuous monitoring is required.