RESUMO
Recent advancements in in vitro transcribed mRNA (IVT-mRNA) vaccine manufacturing have attracted considerable interest as advanced methods for combating viral infections. The respiratory mucosa is a primary target for pathogen attack, but traditional intramuscular vaccines are not effective in generating protective ion mucosal surfaces. Mucosal immunization can induce both systemic and mucosal immunity by effectively eliminating microorganisms before their growth and development. However, there are several biological and physical obstacles to the administration of genetic payloads, such as IVT-mRNA and DNA, to the pulmonary and nasal mucosa. Nucleic acid vaccine nanocarriers should effectively protect and load genetic payloads to overcome barriers i.e., biological and physical, at the mucosal sites. This may aid in the transfection of specific antigens, epithelial cells, and incorporation of adjuvants. In this review, we address strategies for delivering genetic payloads, such as nucleic acid vaccines, that have been studied in the past and their potential applications.
Assuntos
Imunidade nas Mucosas , Nanopartículas , Vacinação , Humanos , Animais , Vacinação/métodos , Vacinas de DNA/imunologia , Vacinas de DNA/administração & dosagem , Vacinas Baseadas em Ácido Nucleico/imunologia , Vacinas Baseadas em Ácido Nucleico/genética , Vacinas Baseadas em Ácido Nucleico/administração & dosagemRESUMO
Epinephelus coioides is a fish species with high economic value due to its delicious meat, high protein content, and rich fatty acid nutrition. It has become a high-economic fish in southern parts of China and some other Southeast Asian countries. In this study, the myostatin nucleic acid vaccine was constructed and used to immunize E. coioides. The results from body length and weight measurements indicated the myostatin nucleic acid vaccine promoted E. coioides growth performance by increasing muscle fiber size. The results from RT-qPCR analysis showed that myostatin nucleic acid vaccine upregulated the expression of myod, myog and p21 mRNA, downregulated the expression of smad3 and mrf4 mRNA. This preliminary study is the first report that explored the role of myostatin in E. coioides and showed positive effects of autologous nucleic acid vaccine on the muscle growth of E. coioides. Further experiments with increased numbers of animals and different doses are needed for its application to E. coiodes aquaculture production.
Assuntos
Fibras Musculares Esqueléticas , Miostatina , Perciformes , Animais , Peso Corporal , Peixes , Regulação da Expressão Gênica , Fibras Musculares Esqueléticas/fisiologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Fatores de Regulação Miogênica/genética , Fatores de Regulação Miogênica/metabolismo , Miogenina/genética , Miogenina/metabolismo , Miostatina/genética , Miostatina/imunologia , Vacinas Baseadas em Ácido Nucleico/administração & dosagem , Vacinas Baseadas em Ácido Nucleico/imunologia , Perciformes/crescimento & desenvolvimento , Perciformes/fisiologia , Proteína Smad3/genética , Proteína Smad3/metabolismo , Vacinação , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismoRESUMO
Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population. Because they are broadly distributed taxonomically, species specific, and stable to genetic manipulation, betaherpesviruses are leading candidates for use as transmissible vaccine vectors. Here we evaluate the likely effectiveness of betaherpesvirus-vectored transmissible vaccines by developing and parameterizing a mathematical model using data from captive and free-living mouse populations infected with murine cytomegalovirus (MCMV). Simulations of our parameterized model demonstrate rapid and effective control for a range of pathogens, with pathogen elimination frequently occurring within a year of vaccine introduction. Our results also suggest, however, that the effectiveness of transmissible vaccines may vary across reservoir populations and with respect to the specific vector strain used to construct the vaccine.
Assuntos
Betaherpesvirinae/genética , Vetores Genéticos/genética , Imunogenicidade da Vacina , Modelos Teóricos , Vacinas Baseadas em Ácido Nucleico/imunologia , Vacinas/imunologia , Algoritmos , Doenças dos Animais/prevenção & controle , Doenças dos Animais/transmissão , Doenças dos Animais/virologia , Animais , Teorema de Bayes , Reservatórios de Doenças , Vetores de Doenças , Vetores Genéticos/imunologia , Infecções por Herpesviridae/veterinária , Camundongos , Muromegalovirus , Vacinas Baseadas em Ácido Nucleico/genética , Prevalência , Vacinas/genéticaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.
Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Nanopartículas/administração & dosagem , SARS-CoV-2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Vacinas contra COVID-19/química , Vacinas contra COVID-19/genética , Cricetinae , Epitopos , Cobaias , Imunogenicidade da Vacina , Camundongos , Nanopartículas/química , Vacinas Baseadas em Ácido Nucleico/administração & dosagem , Vacinas Baseadas em Ácido Nucleico/química , Vacinas Baseadas em Ácido Nucleico/genética , Vacinas Baseadas em Ácido Nucleico/imunologia , Polissacarídeos/química , Polissacarídeos/genética , Polissacarídeos/imunologia , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Potência de VacinaRESUMO
In the age of COVID, nucleic acid vaccines have garnered much attention, at least in part, because of the simplicity of construction, production, and flexibility to adjust and adapt to an evolving outbreak. Orthopoxviruses remain a threat on multiple fronts, especially as emerging zoonoses. In response, we developed a DNA vaccine, termed 4pox, that protected nonhuman primates against monkeypox virus (MPXV)-induced severe disease. Here, we examined the protective efficacy of the 4pox DNA vaccine delivered by intramuscular (i.m.) electroporation (EP) in rabbits challenged with aerosolized rabbitpox virus (RPXV), a model that recapitulates the respiratory route of exposure and low dose associated with natural smallpox exposure in humans. We found that 4pox-vaccinated rabbits developed immunogen-specific antibodies, including neutralizing antibodies, and did not develop any clinical disease, indicating protection against aerosolized RPXV. In contrast, unvaccinated animals developed significant signs of disease, including lesions, and were euthanized. These findings demonstrate that an unformulated, nonadjuvanted DNA vaccine delivered i.m. can protect against an aerosol exposure. IMPORTANCE The eradication of smallpox and subsequent cessation of vaccination have left a majority of the population susceptible to variola virus or other emerging poxviruses. This is exemplified by human monkeypox, as evidenced by the increase in reported endemic and imported cases over the past decades. Therefore, a malleable vaccine technology that can be mass produced and does not require complex conditions for distribution and storage is sought. Herein, we show that a DNA vaccine, in the absence of a specialized formulation or adjuvant, can protect against a lethal aerosol insult of rabbitpox virus.
Assuntos
Vacinas Baseadas em Ácido Nucleico/imunologia , Orthopoxvirus/imunologia , Infecções por Poxviridae/prevenção & controle , Vaccinia virus/imunologia , Vacínia/prevenção & controle , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Relação Dose-Resposta Imunológica , Eletroporação , Feminino , Imunização/métodos , Imunogenicidade da Vacina , Ativação Linfocitária/imunologia , Vacinas Baseadas em Ácido Nucleico/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/imunologia , Coelhos , Vacinas de DNA/imunologia , Vaccinia virus/genética , Vacinas Virais/administração & dosagemRESUMO
Staphylococcus aureus is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against S. aureus have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Translational science studies are attempting to discover correlates of protection using animal models as well as in vitro and ex vivo models assessing efficacy of vaccine candidates. Several new vaccine candidates are being tested in human clinical trials in a variety of target populations. In addition to vaccines, bacteriophages, monoclonal antibodies, centyrins and new classes of antibiotics are being developed. Some of these have been tested in humans with encouraging results. The complexity of the diseases and the range of the target populations affected by this pathogen will require a multipronged approach using different interventions, which will be discussed in this review.