RESUMO
The emergence of the Coronavirus Disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has led to an unprecedented pandemic, which demands urgent development of antiviral drugs and antibodies; as well as prophylactic approaches, namely vaccines. Algae biotechnology has much to offer in this scenario given the diversity of such organisms, which are a valuable source of antiviral and anti-inflammatory compounds that can also be used to produce vaccines and antibodies. Antivirals with possible activity against SARS-CoV-2 are summarized, based on previously reported activity against Coronaviruses or other enveloped or respiratory viruses. Moreover, the potential of algae-derived anti-inflammatory compounds to treat severe cases of COVID-19 is contemplated. The scenario of producing biopharmaceuticals in recombinant algae is presented and the cases of algae-made vaccines targeting viral diseases is highlighted as valuable references for the development of anti-SARS-CoV-2 vaccines. Successful cases in the production of functional antibodies are described. Perspectives on how specific algae species and genetic engineering techniques can be applied for the production of anti-viral compounds antibodies and vaccines against SARS-CoV-2 are provided.
Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Chlamydomonas reinhardtii/genética , Infecções por Coronavirus/tratamento farmacológico , Lectinas/farmacologia , Pneumonia Viral/tratamento farmacológico , Polifenóis/farmacologia , Polissacarídeos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , COVID-19 , Vacinas contra COVID-19 , Núcleo Celular/química , Núcleo Celular/genética , Núcleo Celular/metabolismo , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/metabolismo , Cloroplastos/química , Cloroplastos/genética , Cloroplastos/metabolismo , Infecções por Coronavirus/prevenção & controle , Engenharia Genética/métodos , Humanos , Lectinas/química , Lectinas/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Polifenóis/química , Polifenóis/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vacinas Virais/biossíntese , Vacinas Virais/farmacologiaRESUMO
There are no FDA licensed vaccines or therapeutics for Venezuelan equine encephalitis virus (VEEV) which causes a debilitating acute febrile illness in humans that can progress to encephalitis. Previous studies demonstrated that murine and macaque monoclonal antibodies (mAbs) provide prophylactic and therapeutic efficacy against VEEV peripheral and aerosol challenge in mice. Additionally, humanized versions of two neutralizing mAbs specific for the E2 glycoprotein, 1A3B-7 and 1A4A-1, administered singly protected mice against aerosolized VEEV. However, no studies have demonstrated protection in nonhuman primate (NHP) models of VEEV infection. Here, we evaluated a chimeric antibody 1A3B-7 (c1A3B-7) containing mouse variable regions on a human IgG framework and a humanized antibody 1A4A-1 containing a serum half-life extension modification (Hu-1A4A-1-YTE) for their post-exposure efficacy in NHPs exposed to aerosolized VEEV. Approximately 24 hours after exposure, NHPs were administered a single bolus intravenous mAb. Control NHPs had typical biomarkers of VEEV infection including measurable viremia, fever, and lymphopenia. In contrast, c1A3B-7 treated NHPs had significant reductions in viremia and lymphopenia and on average approximately 50% reduction in fever. Although not statistically significant, Hu-1A4A-1-YTE administration did result in reductions in viremia and fever duration. Delay of treatment with c1A3B-7 to 48 hours post-exposure still provided NHPs protection from severe VEE disease through reductions in viremia and fever. These results demonstrate that post-exposure administration of c1A3B-7 protected macaques from development of severe VEE disease even when administered 48 hours following aerosol exposure and describe the first evaluations of VEEV-specific mAbs for post-exposure prophylactic use in NHPs. Viral mutations were identified in one NHP after c1A3B-7 treatment administered 24 hrs after virus exposure. This suggests that a cocktail-based therapy, or an alternative mAb against an epitope that cannot mutate without resulting in loss of viral fitness may be necessary for a highly effective therapeutic.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Neutralizantes/farmacologia , Encefalomielite Equina Venezuelana/imunologia , Vacinas Virais/farmacologia , Animais , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/imunologia , Modelos Animais de Doenças , Encefalomielite Equina Venezuelana/prevenção & controle , Humanos , Macaca fascicularis , Vacinas Virais/imunologiaRESUMO
Venezuelan equine encephalitis virus (VEEV) is a known biological defense threat. A live-attenuated investigational vaccine, TC-83, is available, but it has a high non-response rate and can also cause severe reactogenicity. We generated two novel VEE vaccine candidates using self-amplifying mRNA (SAM). LAV-CNE is a live-attenuated VEE SAM vaccine formulated with synthetic cationic nanoemulsion (CNE) and carrying the RNA genome of TC-83. IAV-CNE is an irreversibly-attenuated VEE SAM vaccine formulated with CNE, delivering a TC-83 genome lacking the capsid gene. LAV-CNE launches a TC-83 infection cycle in vaccinated subjects but eliminates the need for live-attenuated vaccine production and potentially reduces manufacturing time and complexity. IAV-CNE produces a single cycle of RNA amplification and antigen expression without generating infectious viruses in subjects, thereby creating a potentially safer alternative to live-attenuated vaccine. Here, we demonstrated that mice vaccinated with LAV-CNE elicited immune responses similar to those of TC-83, providing 100% protection against aerosol VEEV challenge. IAV-CNE was also immunogenic, resulting in significant protection against VEEV challenge. These studies demonstrate the proof of concept for using the SAM platform to streamline the development of effective attenuated vaccines against VEEV and closely related alphavirus pathogens such as western and eastern equine encephalitis and Chikungunya viruses.
Assuntos
Vírus da Encefalite Equina Venezuelana/imunologia , Encefalomielite Equina Venezuelana/tratamento farmacológico , Amplificação de Genes , Imunogenicidade da Vacina , RNA Mensageiro/genética , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/uso terapêutico , Células A549 , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Emulsões/química , Encefalomielite Equina Venezuelana/virologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transfecção , Vacinas Virais/farmacologia , Replicação ViralRESUMO
Commercially available saponins are extracted from Quillaja saponaria barks, being Quil A® the most widely used. Nanoparticulate immunostimulating complexes (ISCOMs or ISCOMATRIX) formulated with these, are able to stimulate strong humoral and cellular immune responses. Recently, we formulated novel ISCOMs replacing QuilA® by QB-90 (IQB-90), a Quillaja brasiliensis leaf-extracted saponin fraction, and reported that IQB-90 improved antigen uptake, and induced systemic and mucosal antibody production, and T-cell responses. However, its mechanism of action remains unclear. In this study we provide a deeper insight into the immune stimulatory properties of QB-90 and ISCOMATRIX-like based on this fraction (IMXQB-90). We show herein that, when used as a viral vaccine adjuvant, QB-90 promotes an "immunocompetent environment". In addition, QB-90 and IMXQB-90 induce immune-cells recruitment at draining-lymph nodes and spleen. Subsequently, we prove that QB-90 or IMXQB-90 stimulated dendritic cells secret IL-1ß by mechanisms involving Caspase-1/11 and MyD88 pathways, implying canonical inflammasome activation. Finally, both formulations induce a change in the expression of cytokines and chemokines coding genes, many of which are up-regulated. Findings reported here provide important insights into the molecular and cellular mechanisms underlying the adjuvant activity of Q. brasiliensis leaf-saponins and its respective nanoparticles.
Assuntos
Adjuvantes Imunológicos , Nanopartículas/química , Quillaja/química , Saponinas , Vacinas Virais , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Caspase 1/imunologia , Caspases/imunologia , Caspases Iniciadoras , Células Dendríticas/imunologia , Cães , Feminino , Interleucina-1beta/imunologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Fator 88 de Diferenciação Mieloide/imunologia , Saponinas/química , Saponinas/farmacologia , Vacinas Virais/química , Vacinas Virais/imunologia , Vacinas Virais/farmacologiaRESUMO
The human metapneumovirus (hMPV) is the second leading cause globally of acute infection of the respiratory tract in children, infecting the upper and lower airways. The hMPV may induce an inappropriate Th2-type immune response, which causes severe pulmonary inflammation, leading to the obstruction of airways. Despite its severe epidemiological relevance, no vaccines are currently available for the prevention of hMPV-induced illness. In this investigation, we demonstrated that immunization of mice with the recombinant hMPV nucleoprotein (hMPV-N) mixed with the AbISCO-100 adjuvant reduced viral replication in lungs following challenge with the virus. We found that immunized mice had reduced weight loss, decreased granulocytes in the lung, an increased level of specific nucleoprotein antibodies of IgG1 and IgG2a-isotypes, and a local profile of Th1/Th17-type cytokines. Our results suggest that immunization with the hMPV-N and the AbISCO-100 adjuvant induces a reduction of viral infection and could be considered for the development of an hMPV vaccine.
Assuntos
Imunização , Metapneumovirus/imunologia , Nucleoproteínas/administração & dosagem , Infecções por Paramyxoviridae/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/classificação , Citocinas/análise , Células Dendríticas/classificação , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Granulócitos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Nucleoproteínas/genética , Nucleoproteínas/isolamento & purificação , Infecções por Paramyxoviridae/prevenção & controle , Pneumonia/virologia , RNA Viral/análise , Vacinas Virais/farmacologia , Redução de PesoRESUMO
Zika virus (ZIKV) is a vector-borne disease that has rapidly spread during the year 2016 in more than 50 countries around the world. If a woman is infected during pregnancy, the virus can cause severe birth defects and brain damage in their babies. The virus can be transmitted through the bites of infected mosquitoes as well as through direct contact from human to human (e.g., sexual contact and blood transfusions). As an intervention for controlling the spread of the disease, we study a vaccination model for preventing Zika infections. Although there is no formal vaccine for ZIKV, The National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health) has launched a vaccine trial at the beginning of August 2016 to control ZIKV transmission, patients who received the vaccine are expected to return within 44 weeks to determine if the vaccine is safe. Since it is important to understand ZIKV dynamics under vaccination, we formulate a vaccination model for ZIKV spread that includes mosquito as well as sexual transmission. We calculate the basic reproduction number of the model to analyze the impact of relatively, perfect and imperfect vaccination rates. We illustrate several numerical examples of the vaccination model proposed as well as the impact of the basic reproduction numbers of vector and sexual transmission and the effect of vaccination effort on ZIKV spread. Results show that high levels of sexual transmission create larger cases of infection associated with the peak of infected humans arising in a shorter period of time, even when a vaccine is available in the population. However, a high level of transmission of Zika from vectors to humans compared with sexual transmission represents that ZIKV will take longer to invade the population providing a window of opportunities to control its spread, for instance, through vaccination.
Assuntos
Epidemias/prevenção & controle , Vacinas Virais/farmacologia , Infecção por Zika virus/prevenção & controle , Animais , Número Básico de Reprodução , Simulação por Computador , Feminino , Humanos , Masculino , Conceitos Matemáticos , Modelos Biológicos , Mosquitos Vetores , Gravidez , Vacinação , Zika virus/imunologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissãoRESUMO
In this study, the immune response induced by a mixture of polysaccharide and nucleic acid extracted from Bacillus Calmette-Guerin (BCG) was evaluated in chickens inoculated with infectious bursal disease virus (IBDV) vaccine. After the mixture was injected intramuscularly at a dose of 0.075, 0.15 or 0.3 mg·kg(-1)·day(-1) for 3 days, the 14-day-old chickens were inoculated with the attenuated IBDV vaccine via intranasal and ocular routes. The relative weight of bursa of Fabricius (BF) and thymus, the serum IBD antibody titer, the CD4+/CD8+ ratio, and the concentrations of IFN-γ, IL-2 and IL-6 in peripheral blood were investigated on days 5, 15 and 25. The IBD antibody titer in BCG-treated groups was higher than in the negative control and only IBD-vaccinated chickens, indicating that the mixture of BCG can significantly enhance chicken humoral response. CD4+/CD8+ and the secretions of IFN-γ, IL-2 and IL-6 were also clearly increased compared with that in the negative control and IBD-vaccinated chickens, indicating that the mixture can also enhance the cell-mediated immune response. The results also showed that the relative weights of BF and thymus increased after chickens were inoculated with BCG, indicating that the BCG mixture can clearly enhance the immunity of IBD-vaccine and can be expected to be viewed as a candidate for a new type of immune adjuvant.
Assuntos
Vacina BCG/imunologia , Infecções por Birnaviridae/veterinária , Vírus da Doença Infecciosa da Bursa/imunologia , Ácidos Nucleicos/imunologia , Polissacarídeos/imunologia , Doenças das Aves Domésticas/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais/sangue , Vacina BCG/química , Vacina BCG/farmacologia , Infecções por Birnaviridae/imunologia , Galinhas/imunologia , Vírus da Doença Infecciosa da Bursa/metabolismo , Masculino , Ácidos Nucleicos/isolamento & purificação , Ácidos Nucleicos/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Doenças das Aves Domésticas/terapia , Distribuição Aleatória , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/farmacologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/farmacologia , Vacinas Virais/imunologia , Vacinas Virais/farmacologiaRESUMO
UNLABELLED: Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n = 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus. IMPORTANCE: Over recent decades, world animal health organizations as well as national sanitary authorities have supported the use of vaccination as an essential component of the official FMD control programs in both endemic and disease-free settings. Very few works studied the local immunity induced by FMD vaccines at the respiratory mucosa, and local responses induced in vaccinated animals after aerosol infection have not been described yet. In this work, we demonstrate for the first time that systemic FMD vaccination (i) induced the early presence of active antigen-specific ASC along the respiratory tract and (ii) prompted a rapid local antibody response in the respiratory mucosa, triggered upon oronasal challenge and congruent with a memory B-cell response. This information may help to understand novel aspects of protective responses induced by current FMD vaccines as well as to provide alternative parameters to establish protection efficiency for new vaccine developments.
Assuntos
Anticorpos Antivirais/imunologia , Vírus da Febre Aftosa/fisiologia , Febre Aftosa/prevenção & controle , Vacinação , Vacinas Virais/farmacologia , Replicação Viral/efeitos dos fármacos , Administração por Inalação , Animais , Células Produtoras de Anticorpos/imunologia , Bovinos , Febre Aftosa/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Vacinas Virais/imunologia , Replicação Viral/imunologiaRESUMO
One hundred and sixty 1-month-old turkey poults were delivered to 40 households in four communities of the State of Yucatan, Mexico. The poults were divided into two populations, one vaccinated and the other non-vaccinated against avian pox. During three months, monthly visits were carried out in order to monitor the appearance of lesions suggesting avian pox in the birds delivered. Each turkey was clinically examined, searching for characteristic avian pox lesions that were classified according to the degree of severity observed. The true incidence rate and the cumulative incidence rate of avian pox were determined and the true incidence and cumulative incidence rates of mortality were determined and the relative risks calculated. The true incidence rates for avian pox in vaccinated and non-vaccinated birds were 1.5 and 1.47 respectively. The cumulative incidence rates were 0.94 and 0.90 for vaccinated and non-vaccinated birds, respectively. The comparison for the whole period between vaccinated and non-vaccinated groups did not show a significant statistical difference for mortality. However, when mortality was compared between vaccinated and non-vaccinated turkeys for each month of the study, there was a statistically significant difference for the first month (relative risk = 0.216, confidence interval 0.069 to 0.676). In addition, when the severity of pox lesions between groups was compared, statistically significant differences were found in favour of the vaccinated birds (P < 0.0001).