RESUMO
Chikungunya virus (CHIKV), transmitted through Aedes mosquitoes, is a significant global health concern. Various vaccine platforms have been explored to combat CHIKV, including formalin inactivation, live-attenuated strains, virus-like particles (VLPs), viral vectors, and mRNA technologies. This umbrella review synthesizes evidence on the safety profiles of vaccine platforms used in Chikungunya vaccines that have been applied in other vaccines, focusing on adverse events of special interest (AESI) in pregnant persons, children, and adolescents. A comprehensive overview of systematic reviews (SRs) was conducted. Results: Seven systematic reviews were included and complemented with primary studies. Vaccines like influenza, human papillomavirus (HPV), and COVID-19, which share platforms with Chikungunya vaccines, showed no significant increase in AESI. Moderate-to high-quality SRs supported favorable safety profiles. Vaccines sharing platforms with Chikungunya vaccines generally exhibit acceptable safety profiles in pregnant persons, children, and adolescents.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Vacinas Virais , Humanos , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Gravidez , Feminino , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Adolescente , Criança , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Vacinas de Partículas Semelhantes a Vírus/administração & dosagemRESUMO
As infants suffer significant morbidity and mortality due to norovirus-related acute gastroenteritis (AGE), we assessed four formulations of the bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in Panamanian and Colombian infants. 360 infants aged 6 weeks to 5 months were randomly allocated to 8 groups to receive three doses of HIL-214 or two doses of HIL-214 and one dose of placebo (Days 1, 56 and 112), where HIL-214 doses contained 15/15, 15/50, 50/50 or 50/150 µg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. Solicited injection-site and systemic adverse events (AE) were collected within 7 days after each dose, unsolicited AEs were collected within 28 days after each, and serious AEs throughout the study. Pan-Ig and histoblood group antigen-blocking antibodies (HBGA) were measured on Days 1, 56, 84, and 140. All formulations were well-tolerated causing mainly mild-to-moderate transient solicited AEs, most frequently local pain and irritability/fussiness, but no vaccine-related serious AEs. Two doses of each formulation induced high titers of high avidity Pan-Ig and also HBGA antibodies; a third dose increased titers against both antigens and the avidity of Pan-Ig antibodies against GII.4c but not against GI.1. Two and three doses of HIL-214 were well-tolerated and induced potent immune responses at 4-6 months of age supporting further clinical assessment to protect against norovirus-related AGE.
Assuntos
Anticorpos Antivirais , Infecções por Caliciviridae , Gastroenterite , Norovirus , Vacinas Virais , Humanos , Lactente , Masculino , Método Duplo-Cego , Feminino , Infecções por Caliciviridae/prevenção & controle , Infecções por Caliciviridae/imunologia , Norovirus/imunologia , Norovirus/genética , Anticorpos Antivirais/sangue , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Vacinas Virais/imunologia , Vacinas Virais/efeitos adversos , Vacinas Virais/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Colômbia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Placebos/administração & dosagemRESUMO
This article uses a compartmental model describing the dynamic of the chikungunya virus in populations of humans and mosquitoes with parameters fitted to the incidence in Brazil to estimate the economic trade-off of vaccination against the virus infection. The model uses time-dependent parameters to incorporate fluctuations in the transmission and the mosquito population across the years. Using the model predictions of symptomatic infections and literature data concerning the proportions of post-acute and chronic cases, the vaccination cost is compared with the disease cost. Numerical results considering different scenarios indicate that vaccination has a limited impact on reducing the disease cost assuming that vaccination is applied uniformly countrywide. We do not consider regional targets. In some scenarios, vaccinating about 10% of the population as early as possible can reduce the disease cost and is more economically efficient. Larger proportions make vaccination not viable.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Vacinação , Humanos , Brasil/epidemiologia , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/economia , Febre de Chikungunya/transmissão , Vírus Chikungunya/imunologia , Vacinação/economia , Vacinação/estatística & dados numéricos , Animais , Vacinas Virais/economia , Vacinas Virais/imunologiaRESUMO
BACKGROUND: Infectious diseases, particularly the Goatpox virus (GTPV) from the Poxviridae family, significantly impact livestock health and agricultural economies, especially in developing regions. Recent GTPV outbreaks in previously eradicated areas underscore the need for effective control measures, with vaccination being the most reliable strategy. This study investigates the effects of administering standard and double doses of live attenuated goatpox vaccine in pregnant Murcia-Granada goats, a non-native breed in Iran, to determine optimal vaccination protocols. RESULTS: In 2018, 400 healthy and pregnant Murcia Granada goats imported from Spain were divided into groups of 200 and vaccinated with either a standard dose (0.5 ml) or a double dose (single 0.9 ml injection) of live attenuated goatpox vaccine. Post-vaccination, the goats were monitored daily for clinical signs of infection, with samples collected for PCR analysis to detect the presence of GTPV strains. In group A, which received the standard vaccine dose, no abortions or vaccine-related side effects were observed, and body temperatures remained normal. In group B, administered a double dose, 37% of the goats experienced abortions, displaying signs of GTPV infection, such as skin lesions (pox lesions) and increased body temperatures. Molecular analysis confirmed the vaccine strain of GTPV as the infection source, ruling out external contamination. Statistical analysis showed no significant differences in abortion rates concerning gestational age or t he age of the pregnant goats. CONCLUSION: The study highlights the importance of adhering to standard vaccine dosages in pregnant Murcia Granada goats to prevent adverse outcomes like abortions. This study emphasizes the necessity to review and revise vaccination protocols tailored to specific breeds and varying maintenance conditions, including pregnancy and outbreak scenarios. These findings stress the necessity for cautious and tailored vaccination strategies to ensure the safety and efficacy of vaccines in different goat breeds.
Assuntos
Capripoxvirus , Doenças das Cabras , Cabras , Infecções por Poxviridae , Vacinação , Vacinas Atenuadas , Vacinas Virais , Animais , Feminino , Gravidez , Doenças das Cabras/prevenção & controle , Doenças das Cabras/virologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Vacinas Atenuadas/administração & dosagem , Infecções por Poxviridae/veterinária , Infecções por Poxviridae/prevenção & controle , Capripoxvirus/imunologia , Vacinação/veterinária , Irã (Geográfico) , Espanha , Aborto Animal/prevenção & controle , Aborto Animal/virologiaRESUMO
Classical swine fever (CSF) is endemic in Cuba and is one of the major health problems of the Cuban swine industry. The current efforts to control the disease in Cuba include vaccination with Porvac®, a subunit marker vaccine. Although the efficacy of Porvac against CSF virus (CSFV) subgenotype 1.4 has been extensively documented, little is known about the ability of the antibodies induced by this vaccine to neutralize other CSFV genotypes. In this study, sera collected from three pigs vaccinated with Porvac were able to efficiently neutralize CSFV strains belonging to genotypes 1, 2, and 3. The findings from this study indicate that additional in vivo studies are warranted to confirm the ability of this vaccine to protect pigs against CSFV genotypes 2 and 3.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus da Febre Suína Clássica , Peste Suína Clássica , Genótipo , Vacinas de Subunidades Antigênicas , Vacinas Virais , Animais , Vírus da Febre Suína Clássica/imunologia , Vírus da Febre Suína Clássica/genética , Suínos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Peste Suína Clássica/prevenção & controle , Peste Suína Clássica/imunologia , Peste Suína Clássica/virologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Cuba , VacinaçãoRESUMO
The high antigenic variability of the foot-and-mouth disease virus (FMDV) represents a challenge for developing prophylactic strategies, stressing the need for research into vaccines offering broad protection against a range of virus strains. Here, the heterotypic cross-reaction using different vaccine schemes against serotype O strains was studied, evaluating the impact of revaccination, antigen dose, and incorporation of additional FMDV serotypes. Naïve cattle were immunized with seven distinct FMDV vaccines, receiving three doses of the same formulation at 0, 28, and 56 days post-primary vaccination (dpv). Serum samples were collected up to 70 dpv and tested by a virus-neutralizing test against serotype O strains from a South American lineage and two strains representative of two Asian lineages. Our results showed that vaccines containing the ME-SA topotype O1/Campos strain developed cross-neutralizing responses against the two Asian viruses after the first vaccination. In contrast, significant heterotypic neutralizing antibody titers against the homologous topotype strain were only found after the second vaccination, indicating that the phylogenic relationship may differ from the antigenic profiles for these two viruses. The amount of the O1/Campos strain and the revaccination were essential factors for neutralization against the homologous- and heterologous-type O FMDV viruses. The strain composition of the vaccine was only relevant for cross-neutralization against one of the Asian strains, suggesting potential intra-serotypic divergences for this pattern.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Doenças dos Bovinos , Reações Cruzadas , Vírus da Febre Aftosa , Febre Aftosa , Sorogrupo , Vacinação , Vacinas Virais , Animais , Bovinos , Vírus da Febre Aftosa/imunologia , Vírus da Febre Aftosa/classificação , Febre Aftosa/prevenção & controle , Febre Aftosa/imunologia , Febre Aftosa/virologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Vacinas Virais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Doenças dos Bovinos/imunologia , Reações Cruzadas/imunologia , Vacinação/veterinária , Testes de Neutralização , Proteção Cruzada/imunologia , FilogeniaRESUMO
BACKGROUND: Classical Swine Fever (CSF) is still one of the most economically important viral diseases of pigs. In endemic countries, the disease is controlled mostly through vaccination; hence, the availability of safe and effective vaccines is of utmost importance. Vaccines intended for application in developing countries must also be thermally stable, since the infrastructure needed to maintain a cold chain in those countries is usually lacking. Porvac® is a second-generation subunit marker vaccine against CSF that has demonstrates to be safe and protective. Previous studies have also shown that the vaccine is stable for 1 week at 37 oC and have a shelf life of at least 36 months at 2-8 oC. The aim of this work was to further explore the accelerated stability of Porvac® by assessing the physicochemical properties of the emulsion, and the safety and immunogenicity of the vaccine subjected to more drastic conditions of thermal stress: (1) 25 oC for 12 months; (2) 30oC and 37 oC for one month and (3) 15 days at 37 °C after the cap of the vials had been needle-punctured. RESULTS: The vaccine subjected to all these conditions did not show significant changes in the physicochemical properties of the emulsion; did not produce local or systemic adverse reactions in pigs, and the chromatographic profile of the recovered antigen was preserved. All vaccinated swine developed neutralizing antibody titers ≥ 1:1000 at 28 days post vaccination. CONCLUSIONS: Porvac® is stable in all the experimental conditions tested, even after cap puncture, and retains the capacity to induce high titers of neutralizing antibodies, well above the threshold of protection. These results reinforce the robustness of the vaccine, and support its use as a very attractive alternative to modified live vaccines in developing countries endemic for CSF.
Assuntos
Peste Suína Clássica , Estabilidade de Medicamentos , Vacinas de Subunidades Antigênicas , Vacinas Virais , Animais , Peste Suína Clássica/prevenção & controle , Suínos , Vacinas Virais/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vírus da Febre Suína Clássica/imunologia , Temperatura Alta , Anticorpos Antivirais/sangueRESUMO
Chikungunya fever is a re-emerging mosquito-borne disease caused by the chikungunya virus (CHIKV) and produces acute arthritis that can progress to chronic disease with arthralgia. The first approved live-attenuated chikungunya vaccine has only recently become available for use in humans in the USA, but the access in endemic regions remains unmet. Here, we exploited the baculovirus display technology to develop a vectored vaccine candidate that exposes the CHIKV membrane proteins E1 and E2 on the baculovirus surface. Using recombinant baculovirus as vector vaccines has both productive and regulatory advantages: they are safe for handling and easy to produce in high titers and are non-pathogenic and non-replicative in mammals but have strong adjuvant properties by inducing humoral and cellular immune responses. CHIKV E1 and E2 envelope proteins with their own signal and transmembrane sequences were expressed on the surface of budded baculovirus virions. Immunization of C57BL/6 mice with non-adjuvanted recombinant baculovirus induced IgG antibodies against E2 with a predominant IgG2c subtype, neutralizing antibodies and a specific IFN-γ CD8+ T-cell response. Immunization with a second dose significantly boosted the antibody response, and mice immunized with two doses of the vaccine candidate were completely protected against challenge with CHIKV showing no detectable viremia or signs of disease. Altogether, baculovirus display of CHIKV envelope proteins served as an efficient vaccine platform against CHIKV.IMPORTANCEThe global spread of chikungunya virus (CHIKV) has disproportionately impacted the Americas that experienced a fourfold increase in 2023 in cases and deaths compared with the same period in 2022. The disease is characterized by acute fever and debilitating joint pain that can become chronic. Despite the socioeconomic burden related to the high morbidity rates of CHIKV infection, a vaccine for CHIKV is currently approved only in the USA. Vaccines are the most effective preventive measure against viral diseases, and advances in the development of different vaccine platforms such as nucleic acids and viral vectors have prompted the rapid deployment of vaccines to contain the COVID-19 pandemic. Here, we report the use of baculovirus display as a strategy for the design of a novel vaccine that provides sterilizing immunity in a mouse model of chikungunya disease. Our results encourage further research regarding the potential of baculovirus as platforms for human vaccine design.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Baculoviridae , Febre de Chikungunya , Vírus Chikungunya , Camundongos Endogâmicos C57BL , Proteínas do Envelope Viral , Vacinas Virais , Animais , Vírus Chikungunya/imunologia , Vírus Chikungunya/genética , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Camundongos , Baculoviridae/genética , Vacinas Virais/imunologia , Vacinas Virais/genética , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunidade Celular , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagemRESUMO
Foot and mouth disease (FMD) is a highly contagious infection caused by FMD-virus (FMDV) that affects livestock worldwide with significant economic impact. The main strategy for the control is vaccination with FMDV chemically inactivated with binary ethylenimine (FMDVi). In FMDV infection and vaccination, B cell response plays a major role by providing neutralizing/protective antibodies in animal models and natural hosts. Extracellular vesicles (EVs) and small EVs (sEVs) such as exosomes are important in cellular communication. EVs secreted by antigen-presenting cells (APC) like dendritic cells (DCs) participate in the activation of B and T cells through the presentation of native antigen membrane-associated to B cells or by transferring MHC-peptide complexes to T cells and even complete antigens from DCs. In this study, we demonstrate for the first time that APC activated with the FMDVi O1 Campos vaccine-antigens secrete EVs expressing viral proteins/peptides that could stimulate FMDV-specific immune response. The secretion of EVs-FMDVi is a time-dependent process and can only be isolated within the first 24 h post-activation. These vesicles express classical EVs markers (CD9, CD81, and CD63), along with immunoregulatory molecules (MHC-II and CD86). With an average size of 155 nm, they belong to the category of EVs. Studies conducted in vitro have demonstrated that EVs-FMDVi express antigens that can stimulate a specific B cell response against FMDV, including both marginal zone B cells (MZB) and follicular B cells (FoB). These vesicles can also indirectly or directly affect T cells, indicating that they express both B and T epitopes. Additionally, lymphocyte expansion induced by EVs-FMDVi is greater in splenocytes that have previously encountered viral antigens in vivo. The present study sheds light on the role of EVs derived from APC in regulating the adaptive immunity against FMDV. This novel insight contributes to our current understanding of the immune mechanisms triggered by APC during the antiviral immune response. Furthermore, these findings may have practical implications for the development of new vaccine platforms, providing a rational basis for the design of more effective vaccines against FMDV and other viral diseases.
Assuntos
Células Apresentadoras de Antígenos , Antígenos Virais , Linfócitos B , Vesículas Extracelulares , Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Vírus da Febre Aftosa/imunologia , Vesículas Extracelulares/imunologia , Linfócitos B/imunologia , Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos Virais/imunologia , Vacinas Virais/imunologia , Proteínas Virais/imunologia , Ativação Linfocitária/imunologia , Células Dendríticas/imunologia , Apresentação de Antígeno/imunologiaRESUMO
Multivalent live-attenuated or inactivated vaccines are often used to control the bovine viral diarrhea disease (BVD). Still, they retain inherent disadvantages and do not provide the expected protection. This study developed a new vaccine prototype, including the external segment of the E2 viral protein from five different subgenotypes selected after a massive screening. The E2 proteins of every subgenotype (1aE2, 1bE2, 1cE2, 1dE2, and 1eE2) were produced in mammalian cells and purified by IMAC. An equimolar mixture of E2 proteins formulated in an oil-in-water adjuvant made up the vaccine candidate, inducing a high humoral response at 50, 100, and 150 µg doses in sheep. A similar immune response was observed in bovines at 50 µg. The cellular response showed a significant increase in the transcript levels of relevant Th1 cytokines, while those corresponding to the Th2 cytokine IL-4 and the negative control were similar. High levels of neutralizing antibodies against the subgenotype BVDV1a demonstrated the effectiveness of our vaccine candidate, similar to that observed in the sera of animals vaccinated with the commercial vaccine. These results suggest that our vaccine prototype could become an effective recombinant vaccine against the BVD.
Assuntos
Anticorpos Antivirais , Doença das Mucosas por Vírus da Diarreia Viral Bovina , Vacinas de Subunidades Antigênicas , Vacinas Sintéticas , Vacinas Virais , Animais , Bovinos , Vacinas Virais/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinas Sintéticas/imunologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Doença das Mucosas por Vírus da Diarreia Viral Bovina/imunologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Ovinos , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Citocinas/metabolismo , Vírus da Diarreia Viral Bovina/imunologia , Vírus da Diarreia Viral Bovina/genética , Vírus da Diarreia Viral Bovina Tipo 1/imunologia , Vírus da Diarreia Viral Bovina Tipo 1/genéticaRESUMO
Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.
Assuntos
Infecções Respiratórias , Vacinas de mRNA , Humanos , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/virologia , Infecções Respiratórias/imunologia , Desenvolvimento de Vacinas , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Vacinas contra COVID-19/imunologia , RNA Mensageiro/genética , RNA Mensageiro/imunologiaRESUMO
Morbillivirus canis (canine distemper virus (CDV)) is recognized as a multihost pathogen responsible for a transmissible disease affecting both domestic and wild animals. A considerable portion of wildlife populations remain unvaccinated due to a lack of safety and immunogenicity data on existing vaccines for the prevention of CDV infection in these species. This review aimed to assess the current state of CDV vaccination research for both domestic and wild animals and to explore novel vaccine candidates through in vivo studies. It also sought to synthesize the scattered information from the extensive scientific literature on CDV vaccine research, identify key researchers in the field, and highlight areas where research on CDV vaccination is lacking. A scoping review was conducted across four databases following the PRISMA-ScR protocol, with information analyzed using absolute and relative frequencies and 95% confidence intervals (CIs) for study number proportions. Among the 2321 articles retrieved, 68 met the inclusion criteria and focused on CDV vaccines in various animal species, such as dogs, ferrets, minks, and mice. Most of the scientific community involved in this research was in the USA, Canada, France, and Denmark. Various vaccine types, including MLV CDV, recombinant virus, DNA plasmids, inactivated CDV, and MLV measles virus (MeV), were identified, along with diverse immunization routes and schedules employed in experimental and commercial vaccines. Safety and efficacy data were summarized. Notably, 37 studies reported postimmunization CDV challenge, primarily in dogs, revealing the survival rates of vaccinated animals. In summary, CDV vaccines generally demonstrate an acceptable safety profile in dogs and show promise as a means of controlling CDV. However, significant gaps in vaccine research persist, particularly concerning wildlife reservoirs, indicating the need for further investigation.
Assuntos
Animais Domésticos , Animais Selvagens , Vírus da Cinomose Canina , Cinomose , Vacinação , Vacinas Virais , Animais , Animais Selvagens/virologia , Vírus da Cinomose Canina/imunologia , Vírus da Cinomose Canina/genética , Vacinas Virais/imunologia , Vacinas Virais/efeitos adversos , Vacinas Virais/administração & dosagem , Cinomose/prevenção & controle , Cinomose/imunologia , Cinomose/virologia , Vacinação/veterinária , Cães , Furões , Camundongos , Imunogenicidade da Vacina , Vison/virologia , Vison/imunologiaRESUMO
Canine parvovirus (CPV-2) is a highly contagious virus affecting dogs worldwide, posing a significant threat. The VP2 protein stands out as the predominant and highly immunogenic structural component of CPV-2. Soon after its emergence, CPV-2 was replaced by variants known as CPV-2a, 2b and 2c, marked by changes in amino acid residue 426 of VP2. Additional amino acid alterations have been identified within VP2, with certain modifications serving as signatures of emerging variants. In Brazil, CPV-2 outbreaks persist with diverse VP2 profiles. Vaccination is the main preventive measure against the virus. However, the emergence of substitutions presents challenges to conventional vaccine methods. Commercial vaccines are formulated with strains that usually do not match those currently circulating in the field. To address this, the study aimed to investigate CPV-2 variants in Brazil, predict epitopes, and design an in silico vaccine tailored to local variants employing reverse vaccinology. The methodology involved data collection, genetic sequence analysis, and amino acid comparison between field strains and vaccines, followed by the prediction of B and T cell epitope regions. The predicted epitopes were evaluated for antigenicity, allergenicity and toxicity. The final vaccine construct consisted of selected epitopes linked to an adjuvant and optimized for expression in Escherichia coli. Structural predictions confirmed the stability and antigenicity of the vaccine, while molecular docking demonstrated interaction with the canine toll-like receptor 4. Molecular dynamics simulations indicated a stable complex formation. In silico immune simulations demonstrated a progressive immune response post-vaccination, including increased antibody production and T-helper cell activity. The multi-epitope vaccine design targeted prevalent CPV-2 variants in Brazil and potentially other regions globally. However, experimental validation is essential to confirm our in silico findings.
Assuntos
Simulação por Computador , Doenças do Cão , Infecções por Parvoviridae , Parvovirus Canino , Vacinas Virais , Parvovirus Canino/imunologia , Parvovirus Canino/genética , Parvovirus Canino/química , Animais , Cães , Doenças do Cão/prevenção & controle , Doenças do Cão/imunologia , Doenças do Cão/virologia , Infecções por Parvoviridae/prevenção & controle , Infecções por Parvoviridae/veterinária , Infecções por Parvoviridae/imunologia , Brasil , Vacinas Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/química , Vacinologia/métodos , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Epitopos/imunologia , Epitopos/genética , Epitopos/química , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/químicaRESUMO
Canine distemper virus (CDV) affects many domestic and wild animals. Variations among CDV genome linages could lead to vaccination failure. To date, there are several vaccine alternatives, such as a modified live virus and a recombinant vaccine; however, most of these alternatives are based on the ancestral strain Onderstepoort, which has not been circulating for years. Vaccine failures and the need to update vaccines have been widely discussed, and the development of new vaccine candidates is necessary to reduce circulation and mortality. Current vaccination alternatives cannot be used in wildlife animals due to the lack of safety data for most of the species, in addition to the insufficient immune response against circulating strains worldwide in domestic species. Computational tools, including peptide-based therapies, have become essential for developing new-generation vaccines for diverse models. In this work, a peptide-based vaccine candidate with a peptide library derived from CDV H and F protein consensus sequences was constructed employing computational tools. The molecular docking and dynamics of the selected peptides with canine MHC-I and MHC-II and with TLR-2 and TLR-4 were evaluated. In silico safety was assayed through determination of antigenicity, allergenicity, toxicity potential, and homologous canine peptides. Additionally, in vitro safety was also evaluated through cytotoxicity in cell lines and canine peripheral blood mononuclear cells (cPBMCs) and through a hemolysis potential assay using canine red blood cells. A multiepitope CDV polypeptide was constructed, synthetized, and evaluated in silico and in vitro by employing the most promising peptides for comparison with single CDV immunogenic peptides. Our findings suggest that predicting immunogenic CDV peptides derived from most antigenic CDV proteins could aid in the development of new vaccine candidates, such as multiple single CDV peptides and multiepitope CDV polypeptides, that are safe in vitro and optimized in silico. In vivo studies are being conducted to validate potential vaccines that may be effective in preventing CDV infection in domestic and wild animals.
Assuntos
Vírus da Cinomose Canina , Cinomose , Vacinas Virais , Vírus da Cinomose Canina/imunologia , Animais , Cães , Vacinas Virais/imunologia , Cinomose/prevenção & controle , Cinomose/imunologia , Simulação de Acoplamento Molecular , Peptídeos/imunologia , Peptídeos/química , Vacinas de Subunidades Antigênicas/imunologia , Proteínas Virais de Fusão/imunologiaRESUMO
This study aims to analyze if the results from different serological assays, used alone or combined, could match the outcome of challenge infection with foot-and-mouth disease virus (FMDV) after vaccination in cattle. Day-of-challenge sera from animals that had been vaccinated 21 days before with monovalent formulations containing inactivated A Iran 96 or A Iran 99 virus strains were used. Challenge and serology were performed with A22 Iraq strain. IgG1 titers and total-IgG avidity indexes were significantly higher in protected animals (p < 0.01) while IgG2-titers were not related to protection (p > 0.05). An IgG1 avidity ELISA was developed to analyze in one step, IgG1 levels and avidity. This assay estimated protection with 96 % accuracy. A strong agreement with challenge results was achieved (K = 0.85), suggesting a role of high-affinity IgG1 in protection against FMDV. These results support the assessment of the single dilution IgG1-Avidity ELISA to predict cross-protection in FMDV-vaccinated cattle.
Assuntos
Anticorpos Antivirais , Afinidade de Anticorpos , Doenças dos Bovinos , Proteção Cruzada , Ensaio de Imunoadsorção Enzimática , Vírus da Febre Aftosa , Febre Aftosa , Imunoglobulina G , Vacinação , Vacinas Virais , Animais , Febre Aftosa/prevenção & controle , Febre Aftosa/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Bovinos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vírus da Febre Aftosa/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas Virais/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/imunologia , Proteção Cruzada/imunologia , Vacinação/métodosRESUMO
Yellow fever (YF) is a disease caused by the homonymous flavivirus that can be prevented by a vaccine containing attenuated viruses. Since some individuals cannot receive this vaccine, the development of alternatives is desirable. Here, we developed a recombinant baculovirus (rBV) surface display platform utilizing a chimeric E-NS1 protein as a vaccine candidate. A pBacPAK9 vector containing the baculoviral GP64 signal peptide, the YFV prM, E, NS1 and the ectodomain of VSV-G sequences was synthesized. This transfer plasmid and the bAcGOZA bacmid were cotransfected into Sf9 cells, and an rBV-E-NS1 was obtained, which was characterized by PCR, WB, IFI and FACS analysis. Mice immunized with rBV-E-NS1 elicited a specific humoral and cellular immune response and were protected after YFV infection. In summary, we have developed an rBV that expresses YFV major antigen proteins on its surface, which opens new alternatives that can be tested in a mouse model.
Assuntos
Anticorpos Antivirais , Baculoviridae , Proteínas não Estruturais Virais , Febre Amarela , Vírus da Febre Amarela , Animais , Baculoviridae/genética , Baculoviridae/imunologia , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vírus da Febre Amarela/imunologia , Vírus da Febre Amarela/genética , Proteínas não Estruturais Virais/imunologia , Proteínas não Estruturais Virais/genética , Febre Amarela/prevenção & controle , Febre Amarela/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Células Sf9 , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Feminino , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Imunidade Celular , Camundongos Endogâmicos BALB C , Imunidade Humoral , Vetores Genéticos/genéticaRESUMO
Background: Canine distemper (CD) is a worldwide spread disease that has been described in 12 families of mammals, especially in the Carnivora order, being better studied in domestic canines where vaccination represents the best means of control. CD is controlled by vaccination, but many cases of the disease still occur in vaccinated animals. Aim: The aim of this work was to study antigen-specific epitopes that can subsidize the development of a new vaccine approach. Methods: Mapping of T cell reactive epitopes for CD virus (CDV) was carried out through enzyme-linked immunospot assays using 119 overlapped synthetic peptides from the viral hemagglutinin protein, grouped in 22 pools forming a matrix to test the immune response of 32 animals. Results: Evaluations using the criteria established to identify reactive pools, demonstrated that 26 animals presented at least one reactive pool, that one pool was not reactive to any animal, and six pools were the most frequent among the reactive peptides. The crisscrossing of the most reactive pools in the matrix revealed nine peptides considered potential candidate epitopes for T cell stimulation against the CDV and those were used to design an in-silico protein, containing also predicted epitopes for B cell stimulation, and further analyzed using immune epitope databases to ensure protein quality and stability. Conclusion: The final in silico optimized protein presents characteristics that qualify it to be used to develop a new prototype epitope-based anti-CDV vaccine.
Assuntos
Vírus da Cinomose Canina , Cinomose , Mapeamento de Epitopos , Vacinas Virais , Vírus da Cinomose Canina/imunologia , Animais , Cinomose/prevenção & controle , Cinomose/imunologia , Cães , Vacinas Virais/imunologia , Epitopos de Linfócito T/imunologia , ELISPOT/veterináriaRESUMO
Bovine viral diarrhea virus (BVDV) infection has a significant economic impact on beef and dairy industries worldwide. Fetal infection with a non-cytopathic strain may lead to the birth of persistently infected (PI) offspring, which is the main event in the epidemiological chain of BVDV infection. This report describes the birth of 99 BVDV-PI heifer calves within 52 days of birth in a regular BVDV-vaccinated Brazilian dairy cattle herd and the subgenotypes of the infecting field strains. This study was conducted in a high-yielding open dairy cattle herd that frequently acquired heifers from neighboring areas for replacement. The farm monitors the birth of PI calves by screening all calves born using an ELISA (IDEXX) for BVDV antigen detection. All calves aged 1-7 days were evaluated. For positive and suspected results, the ELISA was repeated when the calves were close to one month old. A total of 294 heifer calves were evaluated between February and March 2021. Of these, 99 (33.7 %) had positive ELISA results and were considered PI calves. To evaluate the predominant BVDV species and subgenotypes in this outbreak, whole blood samples were collected from 31 calves born during the study period. All samples were submitted to the RT-PCR assay for the partial amplification of the BVDV 5'-UTR region, and these amplicons were subjected to nucleotide sequencing. Phylogenetic analysis identified BVDV-1b and BVDV-1d in 16 and 13 heifer calves, respectively. In two calves, it was not possible to determine the BVDV-1 subgenotype. Detection of PI animals and monitoring of circulating BVDV subgenotype strains are central to disease control. This study shows that regular BVDV vaccination alone may be insufficient to prevent BVDV infection in high-yielding open dairy cattle herds. Other biosecurity measures must be adopted to avoid the purchase of cattle with acute infections by BVDV or BVDV-PI, which can cause a break in the health profile of the herd and economic losses.
Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina , Vírus da Diarreia Viral Bovina Tipo 1 , Vírus da Diarreia Viral Bovina , Surtos de Doenças , Filogenia , Animais , Bovinos , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/epidemiologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Surtos de Doenças/veterinária , Feminino , Vírus da Diarreia Viral Bovina Tipo 1/genética , Vírus da Diarreia Viral Bovina Tipo 1/classificação , Vírus da Diarreia Viral Bovina Tipo 1/isolamento & purificação , Vírus da Diarreia Viral Bovina Tipo 1/imunologia , Brasil/epidemiologia , Vírus da Diarreia Viral Bovina/genética , Vírus da Diarreia Viral Bovina/classificação , Vírus da Diarreia Viral Bovina/isolamento & purificação , Vírus da Diarreia Viral Bovina/imunologia , Genótipo , Vacinas Virais/imunologia , Ensaio de Imunoadsorção Enzimática , Indústria de Laticínios , Vacinação/veterinária , Anticorpos Antivirais/sangueRESUMO
Porcine epidemic diarrhea virus (PEDV) has affected the pork industry worldwide and during outbreaks the mortality of piglets has reached 100%. Lipid nanocarriers are commonly used in the development of immunostimulatory particles due to their biocompatibility and slow-release delivery properties. In this study, we developed a lipid nanoparticle (LNP) complex based on glycyrrhizinic acid (GA) and tested its efficacy as an adjuvant in mice immunized with the recombinant N-terminal domain (NTD) of porcine epidemic diarrhea virus (PEDV) spike (S) protein (rNTD-S). The dispersion stability analysis (Z-potential -27.6 mV) confirmed the size and charge stability of the LNP-GA, demonstrating that the particles were homogeneously dispersed and strongly anionic, which favors nanoparticles binding with the rNTD-S protein, which showed a slightly positive charge (2.11 mV) by in silico analysis. TEM image of LNP-GA revealed nanostructures with a spherical-bilayer lipid vesicle (~100 nm). The immunogenicity of the LNP-GA-rNTD-S complex induced an efficient humoral response 14 days after the first immunization (p < 0.05) as well as an influence on the cellular immune response by decreasing serum TNF-α and IL-1ß concentrations, which was associated with an anti-inflammatory effect.