The Challenge of Parasite Control
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2015
Regardless of parasite type—viral, bacterial, or eukaryotic—vaccines tend to fall into one of several categories. Until recently, almost all vaccines could be accurately described as either killed or live, attenuated vaccines (Table 9.6). Killed vaccines (also called inactivated vaccines), as the name suggests, consist of inactivated virus or dead organisms. The Salk polio vaccine and the injected, inactivated influenza vaccines are examples of killed vaccines. Live, attenuated vaccines contain a weakened strain of the parasite, which although able to infect and replicate in the host, is unable to cause disease. The oral Sabin polio vaccine and the more recent attenuated influenza vaccine inhaled as a nasal mist both consist of an attenuated virus. Both types of vaccines have advantages and disadvantages. An attenuated vaccine more closely mimics natural disease and is more likely to stimulate both humoral and cell-mediated immunity. Furthermore, such vaccines are administered through the normal portal of entry and are therefore more likely to generate immunity at the exact site where the parasite is found in the body. There is, however, a low but often significant probability that the attenuated organisms in a live vaccine will revert to virulence if they undergo random mutation. Attenuated polio virus in the Sabin vaccine, for instance, reverts to virulence in about one in each 2.6 million vaccinated individuals, causing symptoms of polio.
The Challenge of Parasite Control
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
Regardless of parasite type—viral, bacterial or eukaryotic—vaccines tend to fall into one of several categories. Until recently, almost all vaccines could be accurately described as either killed or live, attenuated vaccines (Table 9.5). Killed vaccines (also called inactivated vaccines), as the name suggests, consist of inactivated virus or dead organisms. The Salk polio vaccine and the injected, inactivated influenza vaccines are examples of killed vaccines. Attenuated vaccines contain a weakened strain of the parasite, which although able to infect and replicate in the host, is unable to cause disease. The oral Sabin polio vaccine and the more recent attenuated influenza vaccine inhaled as a nasal mist both consist of an attenuated virus. Both types of vaccines have advantages and disadvantages. An attenuated vaccine more closely mimics natural disease and is more likely to stimulate both humoral and cell-mediated immunity. Furthermore, such vaccines are administered through the normal portal of entry and are therefore more likely to generate immunity at the exact site where the parasite is found in the body. There is, however, a low but often significant probability that the attenuated organisms in a live vaccine will revert to virulence if they undergo random mutation. Attenuated poliovirus in the Sabin vaccine, for instance, reverts to virulence in about one in each 2.6 million vaccinated individuals, causing symptoms of polio.
Postherpetic Neuralgia
Gary W. Jay in Practical Guide to Chronic Pain Syndromes, 2016
This live, attenuated varicella vaccine was developed with the goal of conferring an immunologic boost to the age-related waning immunity of older adults. This is especially important in light of the fact that natural immune boosting opportunities will eventually decline as mentioned above. The Shingles Prevention Study—a large, multicenter, randomized, placebo-controlled trial—was conducted to evaluate the efficacy and safety of herpes zoster vaccination (46). The results of the trial indicated that the herpes zoster vaccine reduces the likelihood of developing herpes zoster in immunocompetent individuals 60 years of age or older. Important results of this study included a decrease in the incidence of herpes zoster by 51.3%, a reduction in the overall burden of illness by 61.1%, and a decrease in the incidence of PHN by 66.5% (47). The effect on decreasing the incidence of herpes zoster was less in older subjects, but the effect on reducing the severity of illness was greater in older subjects. Therefore, the overall reduction in burden of illness, the primary end point of the study, was maintained across all age groups. On the basis of these data, the FDA approved the use of the herpes zoster vaccine in individuals 60 years and older. This live, attenuated vaccine is contraindicated in children, pregnant women, and immunocompromised individuals.
Respiratory syncytial virus vaccine: where are we now and what comes next?
Published in Expert Opinion on Biological Therapy, 2018
An overview of different vaccine development strategies and the present vaccine candidates is listed below. A snapshot of the current RSV landscape is provided below (Figure 1): Live attenuated vaccine: Live-attenuated RSV vaccines to protect the pediatric population from RSV disease have been in development for decades. They are attractive vaccine candidates as they offer several advantages for immunization of infants and young children: (1) they do not cause vaccine-associated enhanced RSV disease; (2) they widely stimulate innate, humoral and cellular immunity, as well as systemic and mucosal immunity in the respiratory tract; (3) they can be delivered intranasally; and (4) they replicate in the upper respiratory tract of young infants despite the presence of passively acquired maternally derived RSV neutralizing antibody [56]. Live attenuated vaccine development faces the challenge of sufficient attenuation to be safe and at the same time able to mount a protective immune response. Several candidates are currently undergoing or recently completed clinical trials. A group of these vaccine candidates have deletions of a large segment of the M2-2 gene. The M2-2 gene mediates the transition from transcription to RNA replication [57].
Vogt–Koyanagi–Harada-like Disease following Yellow Fever Vaccination
Published in Ocular Immunology and Inflammation, 2021
Wesley R. Campos, Sarah P. F. Cenachi, Matheus Schmidt Soares, Priscila Freitas Gonçalves, Daniel V. Vasconcelos-Santos
Brazil has recently faced the two largest outbreaks of yellow fever in its history, essentially associated with the periurban sylvatic transmission, but raising concern on risk of urban dissemination through Aedes aegyptii mosquitoes, which have been also implicated in recent outbreaks of Zika virus, chikungunya, and dengue in Brazil and in other countries.2 The best method to prevent/control yellow fever is vaccination, and today, the vaccines are made up of live-attenuated viruses, derived from two substrains, 17D and 17D-204. Adverse effects are not infrequent, but generally mild and well tolerated, including headache, myalgia, and fever, developing in up to 25% of the vaccinated patients. Among the serious but rare adverse effects, a multisystem disease (yellow fever vaccine-associated viscerotropic disease) and a neurological disease (yellow fever vaccine-associated neurologic disease) are of special concern. Both are consequences of infection by the attenuated vaccine virus. Some presumed autoimmune manifestations have also been described, such as Guillain–Barré or acute disseminated encephalomyelitis.3 It is believed that antigen mimicry may trigger an autoimmune response in genetically predisposed individuals.
From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection
Published in Expert Review of Vaccines, 2021
Greta Volpedo, Ryan H Huston, Erin A Holcomb, Thalia Pacheco-Fernandez, Sreenivas Gannavaram, Parna Bhattacharya, Hira L Nakhasi, Abhay R Satoskar
First, there is a concern about the balance between safety and efficacy. Live attenuated vaccines can achieve attenuation by either physicochemical methods (i.e. long-term invitro culture, mutagenesis, or irradiation) or by genetic modifications. In the first case, there is the concern that the parasites could regain virulence; this is also possible for parasites with mutations in just one allele of the genes [203]. Laboratory-generated Leishmania mutants are also antibiotic resistant, which is a useful and practical method for parasite selection during scientific research. Some parasites may retain those genes, which can also lead to antibiotic resistance within Leishmania populations, making this type of vaccine not feasible for clinical use [234]. Thus, homozygous mutants without antibiotic resistance genes would be ideal candidates for safe use in humans. Additionally, live attenuated vaccines should be designed to be safe for immunocompromised patients, since vaccination is also necessary in regions with high rates of HIV-positive individuals [203]. On that regard, killed parasites may appear as a safer alternative, providing a broad range of antigens without the risk of virulence. However, they fail to provide significant protection, suggesting that a carefully designed live attenuated vaccine could be a better option [131].
Related Knowledge Centers
- Adaptive Immune System
- Antibody
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- Vaccine
- Mumps Vaccine
- Rubella Vaccine
- Yellow Fever Vaccine