RESUMO
The outbreak of COVID-19 has posed a serious threat to global public health. Vaccination may be the most effective way to prevent and control the spread of the virus. The safety of vaccines is the focus of preclinical research, and the repeated dose toxicity test is the key safety test to evaluate the vaccine before clinical trials. The purpose of this study was (i) to observe the toxicity and severity of an inactivated SARS-CoV-2 vaccine (Vero cells) in rodent Sprague Dawley rats after multiple intramuscular injections under the premise of Good Laboratory Practice principles and (ii) to provide a basis for the formulation of a clinical trial scheme. The results showed that all animals in the experimental group were in good condition, no regular changes related to the vaccine were found in the detection of various toxicological indexes, and no noticeable stimulating reaction related to the vaccine was found in the injected local tissues. The neutralizing antibodies in the low- and high-dose vaccine groups began to appear 14 days after the last administration. In the negative control group, no neutralizing antibodies were observed from the administration period to the recovery period. Therefore, the repeated administration toxicity test of the inactivated SARS-CoV-2 vaccine (Vero cells) in Sprague Dawley rats showed no obvious toxic reaction. It was preliminarily confirmed that the vaccine can stimulate production of neutralizing antibodies and is safe in Sprague Dawley rats.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Animais , COVID-19 , Vacinas contra COVID-19/toxicidade , Feminino , Masculino , Ratos Sprague-Dawley , Testes de Toxicidade , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/toxicidadeRESUMO
COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2 + mice.
Assuntos
Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina , Vacinas de Produtos Inativados/imunologia , Animais , Vacinas contra COVID-19/toxicidade , Feminino , Raios gama , Genoma Viral , Humanos , Masculino , Camundongos Endogâmicos BALB C , SARS-CoV-2/genética , Vacinas de Produtos Inativados/toxicidadeRESUMO
This study dealt with the toxicity of inactivated bacteria intended for veterinary autogenous vaccines toward a suitable control assay. Two in vitro methods were used. The [3-(4, 5 -dimethylthiazol-2-yl) -2,5 -diphenyltetrazolium bromide] (MTT) test, based on the metabolic reaction of a tetrazolium salt in vital cells, was adopted on the basis of previous positive results. The Interleukin (IL)-1 beta release assay on monocyte-derived pig macrophages was carried out for comparative purposes, to evaluate the possible role of the inflammatory response. MTT and IL-1 beta responses showed a significant correlation (P < 0.05) at defined test dilutions of bacterial antigens, whereas no correlation was demonstrated using MTT responses normalized on bacterial cell concentration. Furthermore, the toxic effects shown in the MTT test were positively correlated to the extracellular protein content. On the whole, the above results could be a useful basis for the development of a toxicity assay on inactivated bacterial vaccines. Also, our data point at bacterial autolysis as a major component underlying toxicity.
Assuntos
Vacinas Bacterianas/toxicidade , Macrófagos/efeitos dos fármacos , Sus scrofa/fisiologia , Testes de Toxicidade , Animais , Técnicas In Vitro , Sais de Tetrazólio/química , Tiazóis/química , Vacinas de Produtos Inativados/toxicidadeRESUMO
The repeated dose toxicity of a prototype cold chain-free, live, attenuated oral cholera vaccine containing 5â¯×â¯106â¯CFU/mL of the VCUSM14P strain was evaluated in Sprague Dawley (SD) rats (single dose administered daily for 30â¯days) to ascertain its safety for clinical use. Repeated dose toxicity studies for cholera vaccines in the literature have administered 2 or 3 fixed doses at 7, 14, 21 or 69â¯day intervals. The present study reports an evaluation of 30 repeated doses of cholera vaccine administered at three different concentrations (Group II (1.25â¯×â¯106â¯CFU), Group III (2.5â¯×â¯106â¯CFU) and Group IV (5â¯×â¯106â¯CFU)) in SD rats. The liquid vaccine was administered orally to the rats with the respective dose every day, and normal saline was administered to the control group (Group I). No significant difference (Pâ¯>â¯0.05) was observed in the body weights and biochemical parameters of the rats after 15 and 30 repeated doses compared to those of the control group. However, compared to those of Group I, a significant increase (Pâ¯<â¯0.05) in the organ to body weight ratios of the lungs, ureter, liver, kidney, heart and spleen was found in G-II, G-III and G-IV. In the haematological analysis, a significant increase in the WBC was observed in G-II and G-IV compared to that in G-I. The histopathological findings indicated mild to moderate degeneration in the liver, kidney, heart and spleen in the treated rats. Mild to moderate lymphocytic infiltration in the lungs was observed in the G-II and G-III rats, and severe infiltration was observed in the G-IV rats. These histopathological findings may be attributed to the 30 doses of vaccine given in daily succession without an interval. In the acute toxicity study, a single dose of vaccine up to 10â¯×â¯106â¯CFU did not cause any adverse effects and lethality in SD rats.
Assuntos
Administração Oral , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/toxicidade , Esquemas de Imunização , Animais , Anticorpos Antibacterianos/sangue , Feminino , Ratos , Ratos Sprague-Dawley , Refrigeração , Testes de Toxicidade Aguda , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/toxicidade , Vibrio choleraeRESUMO
For induction of an appropriate immune response, especially in the case of an inactivated vaccine, the use of an adjuvant is crucial. In this study, adjuvanticity effect of G2 dendrimer in veterinary rabies vaccine has been investigated. A nonlinear globular G2 dendrimer comprising citric acid and polyethylene glycol 600 (PEG-600) was synthesized and the toxicity was studied in vitro on the J774A.1 cell line. The adjuvanticity effect of the dendrimer was then investigated on rabies virus in NMRI mice as a model. Different concentrations of dendrimer were used to determine the best formulation for the survival of the mice after virus challenge. The rise of neutralizing antibody was also checked by rapid fluorescent focus inhibition test (RFFIT). The relative potency of the prepared formulation was finally calculated using standard NIH test and the results were compared (and discussed) with the commercially available rabies vaccine. The accuracy of dendrimer synthesis was confirmed using Fourier transform infrared (FT-IR), size, and zeta potential analysis. The in vitro toxicity assay revealed that no significant toxic effect is observed in cells when data are compared with the control group. The in vivo assay showed that a higher survival rate in the mice received a special formulation due to adjuvanticity effect of dendrimer, which is also confirmed by RFFIT. However, the relative potency of that formulation does not give expected results when compared with the alum-containing rabies vaccine. In the current investigation, the adjuvanticity effect of G2 dendrimer was demonstrated for the first time in rising of neutralizing antibodies against rabies virus. Our data confirm that nanoparticles can enhance immune responses in an appropriate manner. Moreover, engineered nanoparticles will enable us to develop novel potent multivalent adjuvants in vaccine technology.
Assuntos
Adjuvantes Imunológicos/química , Ácido Cítrico/imunologia , Vacina Antirrábica/imunologia , Vírus da Raiva/imunologia , Raiva/veterinária , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/síntese química , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linhagem Celular , Ácido Cítrico/química , Dendrímeros/administração & dosagem , Dendrímeros/síntese química , Dendrímeros/química , Modelos Animais de Doenças , Dose Letal Mediana , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Testes de Neutralização , Polietilenoglicóis/química , Raiva/prevenção & controle , Vacina Antirrábica/administração & dosagem , Vacina Antirrábica/toxicidade , Taxa de Sobrevida , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/toxicidade , Medicina VeterináriaRESUMO
Here we further investigate the pharmacological and toxicological properties of a cholera vaccine based on inactivated whole cells presented in either enteric coated (COA) or uncoated (U/C) tablet formulation from Vibrio cholerae C7258 strain. Tablets were dispersed in 2mL drinking water and administered orally to Sprague Dawley rats distributed in five groups (I COA7, II U/C7 immunized at 0, 7, 69days and III COA14, IV U/C14 immunized at 0, 14, 69days and V control group). Serum vibriocidal antibody response was measured after the administration of two doses with an interval of 7-14days. To further investigate the toxicological aspects a third dose was applied 10 weeks after the initial one. Animals were observed daily and water and food consumption was measured every other day. Periodic blood extractions were performed for hematology, biochemistry, and the titer of serum vibriocidal antibodies was determined. Anatomopathological analysis was performed at days 3 or 14 after the third dose. Results from clinical observations, as well as from water and food consumption and body weigh indicated no toxicity of the vaccine product. Meanwhile, no biological differences were found among different groups in hematological, hemo-chemistry, and anatomopathological studies. Moreover, enteric coated and uncoated tablets against human cholera were found to induce an immune response in rats.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/toxicidade , Feminino , Imunização , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Comprimidos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/toxicidade , Vibrio cholerae/imunologiaRESUMO
Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine or RSV G glycoprotein results in enhanced pulmonary disease after live RSV infection. Enhanced pulmonary disease is characterized by pulmonary eosinophilia and is associated with a substantial inflammatory response. We show that the absence of the G glycoprotein or G glycoprotein CX3C motif during FI-RSV vaccination or RSV challenge of FI-RSV-vaccinated mice, or treatment with anti-substance P or anti-CX3CR1 antibodies, reduces or eliminates enhanced pulmonary disease, modifies T-cell receptor Vbeta usage, and alters CC and CXC chemokine expression. These data suggest that the G glycoprotein, and in particular the G glycoprotein CX3C motif, is key in the enhanced inflammatory response to FI-RSV vaccination, possibly through the induction of substance P.
Assuntos
Quimiocinas CX3C/metabolismo , Proteínas de Membrana , Eosinofilia Pulmonar/etiologia , Receptores de Quimiocinas/metabolismo , Vírus Sinciciais Respiratórios/imunologia , Substância P/biossíntese , Proteínas Virais/fisiologia , Vacinas Virais/toxicidade , Motivos de Aminoácidos , Animais , Linfócitos T CD4-Positivos/imunologia , Receptor 1 de Quimiocina CX3C , Movimento Celular , Quimiocinas/genética , Feminino , Formaldeído , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análise , Receptores de Antígenos de Linfócitos T alfa-beta/fisiologia , Vacinação/efeitos adversos , Vacinas de Produtos Inativados/toxicidade , Proteínas Virais/químicaRESUMO
Prevention of respiratory syncytial virus (RSV) disease will implicate neonatal priming. However, neonatal antigen exposure frequently results into Th2-like responses, some of which are critical for formalin-inactivated RSV (FI-RSV)-associated lung immunopathology. Neonatal immunization of mice may thus represent a more stringent model of RSV-enhanced pathology than adults. Indeed, after RSV challenge, lung cell infiltration, lymphocyte activation, and eosinophilia were higher following neonatal compared with adult FI-RSV priming of BALB/c mice. Unexpectedly, similar findings were obtained with Al(OH)(3)-adsorbed live RSV. In contrast, neonatal priming with BBG2Na, a recombinant RSV subunit vaccine candidate, formulated in either Al(OH)(3) or TiterMax (a Th1-driving adjuvant) resulted in predominant Th2- or Th1-like responses, respectively, but never elicited lung immunopathology post-challenge. Importantly, our data emphasize that the induction of Th2-like responses by RSV subunit vaccines do not necessarily imply lung immunopathology.
Assuntos
Pulmão/patologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/toxicidade , Vacinas de Produtos Inativados/imunologia , Animais , Animais Recém-Nascidos , Anticorpos Antivirais/sangue , Linfócitos T CD4-Positivos/imunologia , Ensaio de Imunoadsorção Enzimática , Formaldeído , Pulmão/efeitos dos fármacos , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas de Produtos Inativados/toxicidadeRESUMO
Binary ethyleneimine (BEI) was used to inactivate the local Egyptian strain of sheep pox virus. The inactivation process was applied using final concentrations of BEI at 0.5, 1, 2 and 3% for different incubation periods at 37 degrees C. The virus was completely inactivated after 7 hours incubation with by 2% BEI final concentration; the inactivated virus was adsorbed on aluminium hydroxide gel when incubated for 6 hours in a concentration 1:1. The antibody levels were estimated by virus neutralization test and ELISA. Specific antibodies appeared from the 1st week post vaccination and remained until the 4th week post challenge. The prepared vaccine was evaluated for safety, sterility and potency. The vaccine proved to be safe, sterile and inducing protection for the vaccinated lambs when challenged by the virulent sheep pox virus up to 6 months post vaccination.
Assuntos
Capripoxvirus/imunologia , Infecções por Poxviridae/veterinária , Doenças dos Ovinos/prevenção & controle , Vacinas Virais/isolamento & purificação , Animais , Aziridinas/farmacologia , Capripoxvirus/efeitos dos fármacos , Camundongos , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/prevenção & controle , Segurança , Ovinos , Doenças dos Ovinos/imunologia , Vacinas de Produtos Inativados/isolamento & purificação , Vacinas de Produtos Inativados/farmacologia , Vacinas de Produtos Inativados/toxicidade , Vacinas Virais/farmacologia , Vacinas Virais/toxicidade , Inativação de Vírus/efeitos dos fármacosRESUMO
The mechanisms by which administration of a formalin-inactivated respiratory syncytial virus vaccine resulted in enhanced disease among children after they later became naturally infected with the virus remains largely undefined. After immunization and live virus challenge, the cotton rat demonstrated the histopathologic marker of the enhanced disease, polymorphonuclear leukocyte infiltration of lung alveolar spaces. We now report that immunization with formalin-inactivated vaccine formulated with the adjuvant, 3-deacylated monophosphoryl lipid A, dramatically reduces or eliminates the polymorphonuclear leukocyte infiltration within the alveoli of cotton rats post-challenge. We suggest, that this or similar adjuvants may be beneficial components of candidate non-replicating respiratory syncytial virus vaccines, whose development has been hampered by safety concerns.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Lipídeo A/administração & dosagem , Vírus Sinciciais Respiratórios/imunologia , Vacinas Virais/efeitos adversos , Vacinas Virais/toxicidade , Animais , Criança , Feminino , Formaldeído , Humanos , Lipídeo A/análogos & derivados , Masculino , Alvéolos Pulmonares/patologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Segurança , Sigmodontinae , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/toxicidadeRESUMO
Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children. Immunopathology may play a role in RSV-induced disease and a severe RSV infection may also be associated with an increased risk of developing asthma. Vaccination with formalin-inactivated RSV (FI-RSV) prior to infection resulted both in human and in the mouse model in extensive lung pathology. In the mouse model, it has been shown that this aggravation of disease was associated with a shift in the balance between Th1 and Th2 cytokines towards a Th2-type response. The aim of the present study was to characterise the immunological and inflammatory responses in BALB/c mice upon RSV infection with or without prior vaccination with aluminium-adjuvanted FI-RSV or control antigens (FI-Mock). As previously reported by others, we also observed that a primary RSV infection in BALB/c mice resulted in a predominant Th1-type cytokine response, which was associated with slight bronchiolitis and alveolitis. FI-RSV vaccination prior to RSV challenge prevented virus replication and was associated with an aggravation of pulmonary histopathology and a shift towards a Th2-type response. Vaccination with FI-Mock did not prevent RSV replication in the lung but resulted in an even more pronounced Th2 response after infection while these mice were not sensitised to specific viral antigens. Thus, viral replication in a Th2 responding animal (induced by aluminium-adjuvanted mock vaccine) appears to boost the Th2 response upon RSV infection.
Assuntos
Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/imunologia , Vírus Sinciciais Respiratórios/patogenicidade , Vacinas Virais/administração & dosagem , Vacinas Virais/toxicidade , Animais , Anticorpos Antivirais/biossíntese , Pré-Escolar , Citocinas/biossíntese , Citocinas/genética , Feminino , Formaldeído , Humanos , Imunização , Lactente , Inflamação/etiologia , Inflamação/patologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sinciciais Respiratórios/fisiologia , Células Th1/imunologia , Células Th2/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/toxicidade , Replicação ViralRESUMO
All the vaccines supplied for the large scale comparative leprosy vaccine trial of ICRC bacilli, M.w, BCG plus killed M. leprae (candidate vaccines), BCG and normal saline (control arms) at CJIL Field Unit, Chennai were tested for quality control by the suppliers following the procedures laid down in the WHO protocol for killed M. leprae. Quality control for BCG was carried out at BCG vaccine laboratory as per protocol. Toxicity and sterility tests were done on all the vaccine batches/lots received. As part of the quality control, bacterial count, and protein estimation were also done. Studies showed that the bacterial content and protein concentration were comparable with the original preparations. Vaccines were free from micro-organisms, toxic materials and safe for human use. Thus the quality of all vaccine preparations was satisfactory.
Assuntos
Vacina BCG/normas , Mycobacterium leprae/efeitos dos fármacos , Controle de Qualidade , Vacina BCG/química , Vacina BCG/toxicidade , Bactérias/isolamento & purificação , Humanos , Índia , Laboratórios , Proteínas/análise , Vacinas de Produtos Inativados/química , Vacinas de Produtos Inativados/normas , Vacinas de Produtos Inativados/toxicidadeRESUMO
The comparative study of the immunogenic and protective properties of V. cholerae, grown in vivo and in vitro, and cell walls and lysates obtained from these organisms. In the mouse protection test the efficacy of preparations obtained from vibrios grown in vivo did not exceed that of the preparations obtained from V. cholerae agar cultures.
Assuntos
Vibrio cholerae/imunologia , Animais , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/toxicidade , Membrana Celular/imunologia , Cólera/prevenção & controle , Meios de Cultura , Relação Dose-Resposta Imunológica , Imunização/métodos , Dose Letal Mediana , Camundongos , Coelhos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/toxicidade , Vibrio cholerae/crescimento & desenvolvimento , Vibrio cholerae/patogenicidade , Virulência/imunologiaRESUMO
As a result of the high-dose gamma-irradiation (50 kGy) of corpuscular pertussis vaccine (CPV), pertussis radiovaccine (PRV) was obtained. Compared with CPV, PRV was shown to possess reduced toxicity and higher protective potency. Its adjuvant properties remained at the initial level, while its leukocytosis-promoting and histamine-sensitizing activities drastically decreased. Moreover, PRV produced less pronounced stimulating effect on the proliferation of hematopoietic stem cells, but, in contrast to CPV, was shown to capable of protecting mice from lethal radiation.
Assuntos
Vacina contra Coqueluche/imunologia , Vacina contra Coqueluche/efeitos da radiação , Animais , Células Produtoras de Anticorpos/imunologia , Raios gama , Células-Tronco Hematopoéticas/imunologia , Histamina/análogos & derivados , Histamina/imunologia , Imunização , Leucocitose/induzido quimicamente , Camundongos , Camundongos Endogâmicos CBA , Vacina contra Coqueluche/toxicidade , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/mortalidade , Tolerância a Radiação/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/efeitos da radiação , Vacinas de Produtos Inativados/toxicidadeRESUMO
Alternative methods for titrating antitoxin are now available which should, in principle, permit a very large reduction in the numbers of animals required to test the potency of toxoid vaccines. More importantly they make it possible to eliminate the use of animals for the indication of excess toxicity almost completely. The full realisation of this potential is dependent upon the careful validation of all other methods and the introduction of more appropriate standard and reference preparations for titration of antisera and for the assay of DTP. It would be facilitated by a mechanism to facilitate the wider dissemination of relevant monoclonal antibodies and by a restructuring of veterinary vaccine potency tests to make full use of the additional serological information provided by the new methods.
Assuntos
Alternativas aos Testes com Animais/métodos , Testes de Neutralização/métodos , Toxoides/farmacologia , Toxoides/toxicidade , Vacinas de Produtos Inativados/farmacologia , Vacinas de Produtos Inativados/toxicidade , Alternativas aos Testes com Animais/normas , Animais , Anticorpos Monoclonais , Antitoxinas , Clostridium/imunologia , Humanos , Técnicas In Vitro , Testes de Neutralização/normas , Padrões de Referência , Toxoides/normas , Vacinas de Produtos Inativados/normas , Organização Mundial da SaúdeRESUMO
Strains X-73 (serotype 1) and P-1059 (serotype 3) of Pasteurella multocida, avian origin, expressed additional membrane proteins (MPs) when grown in brain-heart infusion (BHI) broth containing the iron chelator dipyridyl and when grown in BHI broth treated with the iron chelator Chelex 100. These additional MPs were not detected when both strains were grown in BHI broth. Chickens and turkeys were vaccinated twice with inactivated oil-emulsion vaccines containing bacterial cells expressing these MPs or with vaccines containing bacterial cells grown in BHI broth. Two weeks after the final vaccination, all birds were challenged to determine whether bacterins made from P. multocida that had been propagated in conditions of iron deprivation would induce heterologous serotype immunity. The bacterins produced in medium low in iron did not consistently induce significant protection against heterologous challenge.
Assuntos
Vacinas Bacterianas/administração & dosagem , Infecções por Pasteurella/veterinária , Pasteurella multocida , Doenças das Aves Domésticas , Vacinas de Produtos Inativados/administração & dosagem , Animais , Proteínas de Bactérias/análise , Vacinas Bacterianas/toxicidade , Galinhas , Meios de Cultura , Eletroforese em Gel de Poliacrilamida , Ferro/metabolismo , Infecções por Pasteurella/prevenção & controle , Pasteurella multocida/classificação , Pasteurella multocida/crescimento & desenvolvimento , Perus , Vacinas de Produtos Inativados/toxicidadeRESUMO
A hepatitis A vaccine was prepared by formaldehyde inactivation of purified hepatitis A virus (HAV) LSH/S strain grown on human diploid MRC-5 cells. The vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. Infectious HAV particles were not detected in faeces and sera of the vaccinated primates by ELISA or after passages in MRC-5 cells. The immunogenicity of the vaccine was evaluated by injecting guinea-pigs with 0.8, 0.2 or 0.05 micrograms of HAV antigen adsorbed onto 0.5 and 1 mg of Al (OH)3 or 0.3 mg of AlPO4. The antibody response, measured by a competitive radioimmunoassay, was dose- and adjuvant-dependent. One injection of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced seroconversion in 100% of animals and high levels of specific and neutralizing serum antibodies. A further increase of antibody titres was observed after the second and third inoculations. These results show that this vaccine formulation is safe and immunogenic in animal models, and suggest that it should be evaluated further by human clinical studies.
Assuntos
Compostos de Alumínio , Vacinas contra Hepatite Viral/isolamento & purificação , Adjuvantes Imunológicos/administração & dosagem , Alumínio/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Animais , Callithrix , Linhagem Celular , Cobaias , Anticorpos Anti-Hepatite A , Vacinas contra Hepatite A , Anticorpos Anti-Hepatite/sangue , Hepatovirus/crescimento & desenvolvimento , Hepatovirus/imunologia , Humanos , Fosfatos/administração & dosagem , Vacinas de Produtos Inativados/isolamento & purificação , Vacinas de Produtos Inativados/farmacologia , Vacinas de Produtos Inativados/toxicidade , Vacinas contra Hepatite Viral/farmacologia , Vacinas contra Hepatite Viral/toxicidadeRESUMO
Two vaccine preparations obtained from Bordetella pertussis, whole-cell vaccine constituting one of the components of adsorbed DPT vaccine and acellular vaccine, were tested for mutagenicity. The doses of the preparations covered the range 1-100 ED50. Ames' test and the metaphase analysis of marrow cells of C57BL/6J mice were used. The acellular preparation was also tested on thymectomized mice, taking into consideration chromosomal aberrations in marrow metaphases. Whole-cell and acellular pertussis vaccines did not induce mutations in Salmonella typhimurium and chromosomal aberrations in mouse marrow cells.
Assuntos
Mutagênese/efeitos dos fármacos , Vacina contra Coqueluche/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/ultraestrutura , Aberrações Cromossômicas , Relação Dose-Resposta a Droga , Genes Bacterianos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Vacinas de Produtos Inativados/toxicidadeRESUMO
Salmonella enterica serovars Typhimurium and Enteritidis are facultative intracellular pathogens which cause in mice a disease similar to human typhoid fever caused by serovar Typhi. An essential phase in the infection process is bacterial replication inside cells of the liver and spleen; the rate of replication is restricted by interferon-gamma (IFN-gamma) produced early in the infection. In the present study the effect of IFN-gamma was neutralized in vivo with monoclonal antibody and the fate of bacteria in the liver and spleen in these mice compared with that in control mice after intravenous challenge. The depletion of IFN-gamma remarkably sensitized the mice to Typhimurium infection. Five different Typhimurium and Enteritidis candidate vaccine strains were tested. Only one of them, the aroA mutant SL3261, was avirulent also in anti-IFN-gamma treated mice. This finding may have important implications for the safety of live attenuated Salmonella vaccines since immunosuppression is likely to cause a state of reduced production of IFN-gamma.