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1.
J Equine Vet Sci ; 133: 104992, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160702

RESUMO

During neurological EHV-1 outbreaks, modified-live vaccines (MLV) are often administrated intranasally in an off-label fashion to healthy cohort horses in order to achieve rapid mucosal immunity. Thus, the goal of the present study was to determine if a commercially available EHV-1 MLV given intranasally to healthy horses would trigger a measurable systemic and/or mucosal antibody response. Eight healthy adult horses were given the EHV-1 MLV vaccine intranasally, while 8 healthy adult horses received the vaccine intramuscularly. An additional 8 healthy horses served as unvaccinated controls. EHV-1 specific antibodies (total IgG, IgG4/7, IgG1 and IgA) were measured in blood and nasal secretions prior to vaccine administration and 14- and 30-days post-vaccine administration. Further, nasal secretions and whole blood were tested for the presence of EHV-1 DNA by qPCR prior to and 5 days after vaccine administration. EHV-1 was detected by qPCR for the first 48 hours post-intranasal vaccine administration in nasal secretions in a total of three horses. Total EHV-1 IgG and IgG4/7 antibody values in serum increased only in horses receiving the intramuscular MLV. Antibody values at 14- and 30-days post vaccine administration were not different from values prior to vaccine administration in horses receiving the intranasal vaccine. The results support the intramuscular use of the EHV-1 MLV as recommended by the manufacturer. Intranasal vaccination with the study-specific EHV-1 MLV did not induce an increase in systemic or nasal antibodies, therefore, this vaccine route seems suboptimal and should not be used to vaccinate adult horses that have received multiple EHV-1 vaccinations and have pre-existing antibodies against EHV-1.


Assuntos
Herpesvirus Equídeo 1 , Vacinas contra Herpesvirus , Humanos , Cavalos , Animais , Herpesvirus Equídeo 1/genética , Anticorpos Antivirais , Vacinação/veterinária , Vacinação/métodos , Imunoglobulina G , Vacinas Atenuadas
2.
Front Immunol ; 14: 1201973, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600784

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a leading cause of economic loss in pig farming worldwide. Existing commercial vaccines, all based on modified live or inactivated PRRSV, fail to provide effective immunity against the highly diverse circulating strains of both PRRSV-1 and PRRSV-2. Therefore, there is an urgent need to develop more effective and broadly active PRRSV vaccines. In the absence of neutralizing antibodies, T cells are thought to play a central role in controlling PRRSV infection. Herpesvirus-based vectors are novel vaccine platforms capable of inducing high levels of T cells against encoded heterologous antigens. Therefore, the aim of this study was to assess the immunogenicity and efficacy of an attenuated herpesvirus-based vector (bovine herpesvirus-4; BoHV-4) expressing a fusion protein comprising two well-characterized PRRSV-1 T-cell antigens (M and NSP5). Prime-boost immunization of pigs with BoHV-4 expressing the M and NSP5 fusion protein (vector designated BoHV-4-M-NSP5) induced strong IFN-γ responses, as assessed by ELISpot assays of peripheral blood mononuclear cells (PBMC) stimulated with a pool of peptides representing PRRSV-1 M and NSP5. The responses were closely mirrored by spontaneous IFN-γ release from unstimulated cells, albeit at lower levels. A lower frequency of M and NSP5 specific IFN-γ responding cells was induced following a single dose of BoHV-4-M-NSP5 vector. Restimulation using M and NSP5 peptides from PRRSV-2 demonstrated a high level of cross-reactivity. Vaccination with BoHV-4-M-NSP5 did not affect viral loads in either the blood or lungs following challenge with the two heterologous PRRSV-1 strains. However, the BoHV-4-M-NSP5 prime-boost vaccination showed a marked trend toward reduced lung pathology following PRRSV-1 challenge. The limited effect of T cells on PRRSV-1 viral load was further examined by analyzing local and circulating T-cell responses using intracellular cytokine staining and proliferation assays. The results from this study suggest that vaccine-primed T-cell responses may have helped in the control of PRRSV-1 associated tissue damage, but had a minimal, if any, effect on controlling PRRSV-1 viral loads. Together, these results indicate that future efforts to develop effective PRRSV vaccines should focus on achieving a balanced T-cell and antibody response.


Assuntos
Vacinas contra Herpesvirus , Imunogenicidade da Vacina , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Proteínas da Matriz Viral , Proteínas não Estruturais Virais , Vacinas contra Herpesvirus/imunologia , Vacinas Atenuadas/imunologia , Linfócitos T/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Vetores Genéticos , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Animais , Suínos , Proteínas da Matriz Viral/imunologia
3.
Elife ; 122023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648132

RESUMO

Background: Both sex and prior exposure to pathogens are known to influence responses to immune challenges, but their combined effects are not well established in humans, particularly in early innate responses critical for shaping subsequent outcomes. Methods: We employed systems immunology approaches to study responses to a replication-defective, herpes simplex virus (HSV) 2 vaccine in men and women either naive or previously exposed to HSV. Results: Blood transcriptomic and cell population profiling showed substantial changes on day 1 after vaccination, but the responses depended on sex and whether the vaccinee was naive or previously exposed to HSV. The magnitude of early transcriptional responses was greatest in HSV naive women where type I interferon (IFN) signatures were prominent and associated negatively with vaccine-induced neutralizing antibody titers, suggesting that a strong early antiviral response reduced the uptake of this replication-defective virus vaccine. While HSV seronegative vaccine recipients had upregulation of gene sets in type I IFN (IFN-α/ß) responses, HSV2 seropositive vaccine recipients tended to have responses focused more on type II IFN (IFN-γ) genes. Conclusions: These results together show that prior exposure and sex interact to shape early innate responses that then impact subsequent adaptive immune phenotypes. Funding: Intramural Research Program of the NIH, the National Institute of Allergy and Infectious Diseases, and other institutes supporting the Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation. The vaccine trial was supported through a clinical trial agreement between the National Institute of Allergy and Infectious Diseases and Sanofi Pasteur. Clinical trial number: NCT01915212.


Assuntos
Vacinas contra Herpesvirus , Imunidade Inata , Fatores Sexuais , Feminino , Humanos , Masculino , Anticorpos Neutralizantes , Herpesvirus Humano 2 , Vacinas contra Herpesvirus/imunologia , Vacinas Atenuadas , Herpes Simples/prevenção & controle
4.
J Equine Vet Sci ; 122: 104229, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36657628

RESUMO

EHV-1 vaccines are often administered intranasally during emergency situation such as outbreaks of equine herpesvirus myeloencephalopathy. However, there is currently no data available on the efficacy of such protocols, nor the diagnostic challenge when recently vaccinated horses become clinically infected and nasal secretions are collected to support a diagnosis of EHV-1 infection. Therefore, the objective of this study was to determine if two commercially available EHV-1 vaccines, a killed-adjuvanted (Calvenza) and a modified-live (Rhinomune) EHV-1 vaccine, could induce a measurable systemic antibody response postintranasal administration. A second objective was to determine the detection time of EHV-1 in nasal secretions by qPCR following the intranasal administration of the respective EHV-1 vaccines. Thirty healthy adult horses, with no recent EHV-1 vaccine administration, were randomly assigned to one of three groups: Rhinomune group, Calvenza group, and unvaccinated control group. Total Ig and isotype-specific IgG4/7 against EHV-1 measured pre- and 30-days post-vaccination were not different amongst the three study groups. Vaccine-derived EHV-1 was only detected in the two EHV-1 vaccine groups with 9/10 horses in the Rhinomune group and 8/10 horses in the Calvenza group testing qPCR-positive for EHV-1 for 1 to 3 days. There was no significant difference in number of horses testing qPCR-positive for EHV-1 and absolute quantitation of EHV-1 in nasal secretions by qPCR between the two vaccine groups. The intranasal administration of two commercial EHV-1 vaccines did not elicit a systemic immune response. Further, vaccine derived EHV-1 could be detected in the majority of the intranasally vaccinated horses, potentially impacting diagnostic interpretation of EHV-1 during outbreak situations.


Assuntos
Herpesvirus Equídeo 1 , Vacinas contra Herpesvirus , Doenças dos Cavalos , Vacinas , Animais , Cavalos , Administração Intranasal/veterinária , Formação de Anticorpos , Anticorpos Antivirais , Doenças dos Cavalos/prevenção & controle
5.
Equine Vet J ; 55(3): 389-404, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35946376

RESUMO

BACKGROUND: Equid herpesvirus type 1 (EHV-1) infection can cause a range of disease syndromes of variable severity that can result in a lethal outcome and restriction of horse movements, especially in the case of outbreaks involving neurological disease. Vaccination is one of the tools used to control the infection. It is widely known that vaccination is not completely effective in ensuring protection against disease caused by this virus. In fact, the real efficacy of vaccination against EHV-1 related disease has not been measured and no systematic reviews exist on this topic. OBJECTIVES: To perform a systematic review and meta-analysis on the efficacy of commercial or candidate vaccines against EHV-1 in randomised controlled trials (RCT) all of which involved experimental challenge of the test subjects. STUDY DESIGN: Systematic review and meta-analysis. METHODS: RCTs were searched using the search algorithm (([equid herpesvirus* OR equine herpesvirus* OR EHV-1]) AND vaccin*) AND (trial OR experimental OR challenge) on PubMed, Science Citation Index Expanded, Scopus, and CAB Abstracts. Where appropriate, meta-analysis was performed using RevMan 5.4. RESULTS: Eight studies were selected and were analysed for their respective characteristics and possible shortcomings. The results of RCTs revealed that there was a general improvement in the clinical and virological outcomes of EHV-1 infection following vaccination, but that the effects were very slight. The reduced beneficial effect is probably amplified by the paucity of detailed data reported in the studies that did not allow for the comparison of parameters in many of the cases analysed. MAIN LIMITATIONS: The remarkable heterogeneity and the poor quality of reporting of the selected studies. CONCLUSIONS: Meta-analysis has shown that EHV-1 vaccination generally results in a slight improvement in clinical and virological outcomes, although not to a significant extent. The cumulative results have probably been affected by the lack of information on some parameters not systematically reported in the studies. An improvement in the standard of reporting and better standardisation of the data collected would likely have improved the quality of each study and enabled more effective comparison of the studies with each other.


Assuntos
Infecções por Herpesviridae , Herpesvirus Equídeo 1 , Vacinas contra Herpesvirus , Doenças dos Cavalos , Animais , Cavalos , Vacinas contra Herpesvirus/uso terapêutico , Anticorpos Antivirais , Vacinação/veterinária , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Doenças dos Cavalos/prevenção & controle
6.
J Equine Vet Sci ; 116: 104051, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35753636

RESUMO

Protection against infectious diseases can be obtained with vaccines generating immunogenic response through a combination of humoral and cellular immunity. In this study haematological and serum protein electrophoretic profiles of horses vaccinated against herpesvirus 1 (EHV-1) and 4 (EHV-4) were evaluated. Blood samples were collected from 16 horses before (T0), after 24h, 48h, 72h, 1st week, 2nd week and 3rd week (T1I, T2I, T3I, T7I, T14I and T21I) from the first EHV vaccine-dose administration as well as before (TPREII), and after 24h, 48h, 72h, 1st week, 2nd week, 3rd week and 4th week (T1II, T2II, T3II, T7II, T14II, T21II and T28II) from the EHV vaccine-booster. Total leukocyte values increased at T1I, T1II, T3II and T28II compared to T0 (P < .01). Higher lymphocytes and lower neutrophils values were found after first vaccine-dose and vaccine-booster administration compared to the T0 (P < .01). Monocytes showed higher values at T14II than T0 (P < .01). Higher serum values of total proteins, α1-, α-2-, ß1-, ß2- and γ-globulins were found in horses after first vaccine-dose and vaccine-booster administration (P < .01). Gathered results suggest that horses vaccinated against EHV1 and EHV-4 exhibited a dynamic change of WBC, lymphocytes, neutrophils and monocytes. Moreover, the analysis of serum electrophoresis pattern suggested that EHV vaccination induced the development of inflammation and antibody response in vaccinated horses as highlighted by the increase of α-, ß- and γ-globulin fractions. These changes probably reflect the systemic immunological adaptation of animals to EHV vaccine.


Assuntos
Infecções por Herpesviridae , Herpesvirus Equídeo 1 , Herpesvirus Equídeo 4 , Vacinas contra Herpesvirus , Doenças dos Cavalos , Animais , Anticorpos Antivirais , Eletroforese/veterinária , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Doenças dos Cavalos/prevenção & controle , Cavalos , Leucócitos
7.
Vet Microbiol ; 268: 109429, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35421830

RESUMO

Herpesvirus of turkeys (HVT), a commonly used live vaccine against Marek's disease, has proven to be a highly effective viral vector for the generation of recombinant vaccines that deliver protective antigens of other avian pathogens. In this study, a vaccine designated rHVT-NDV-opti F was constructed by inserting a codon-optimized genotype Ⅶ Newcastle disease virus (NDV) fusion (F) gene into the US2 gene of HVT Fc126 vaccine strain using CRISPR/Cas9 gene-editing technology coupled with two single-guide RNAs (sgRNA). The F protein expression of rHVT-NDV-opti F was detectable by western blotting and an indirect immunofluorescence assay. Compared with wildtype HVT, rHVT-NDV-opti F has similar plaque morphology but lower in vitro replication capacity. The F protein of rHVT-NDV-opti F is genetically stable and predominantly expressed in the cell plasma. Immunization of one-day-old specific pathogen-free chickens with 4000 plaque-forming units of rHVT-NDV-opti F induced NDV-specific antibodies and provided 70% protection against a homologous NDV challenge, effectively reducing virus shedding, clinical signs, tissue viral load, and mortality. These results suggest that rHVT-NDV-opti F could be a potential vaccine candidate against Newcastle disease in chickens and that HDR-CRISPR/Cas9 combined with dual sgRNA can rapidly and efficiently construct HVT-vectored vaccine candidates.


Assuntos
Herpesvirus Galináceo 2 , Vacinas contra Herpesvirus , Doença de Newcastle , Doenças das Aves Domésticas , Vacinas Virais , Animais , Anticorpos Antivirais , Galinhas , Genótipo , Herpesvirus Meleagrídeo 1/genética , Herpesvirus Galináceo 2/genética , Vírus da Doença de Newcastle/genética , Doenças das Aves Domésticas/prevenção & controle , Proteínas Recombinantes de Fusão/genética , Perus , Vacinas Sintéticas
8.
Viruses ; 14(2)2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35215786

RESUMO

The Varicella-zoster virus (VZV) or human herpes virus 3 is a neurotropic human alpha herpes virus responsible for chickenpox/varicella and shingles/Herpes zoster (HZ). This review will focus on HZ. Since HZ is secondary to varicella, its incidence increases with age. In children and youngsters, HZ is rare and associated to metabolic and neoplastic disorders. In adults, advanced age, distress, other infections (such as AIDS or COVID-19), and immunosuppression are the most common risk factors. HZ reactivation has recently been observed after COVID-19 vaccination. The disease shows different clinical stages of variable clinical manifestations. Some of the manifestations bear a higher risk of complications. Among the possible complications, postherpetic neuralgia, a chronic pain disease, is one of the most frequent. HZ vasculitis is associated with morbidity and mortality. Renal and gastrointestinal complications have been reported. The cornerstone of treatment is early intervention with acyclovir or brivudine. Second-line treatments are available. Pain management is essential. For (secondary) prophylaxis, currently two HZV vaccines are available for healthy older adults, a live attenuated VZV vaccine and a recombinant adjuvanted VZV glycoprotein E subunit vaccine. The latter allows vaccination also in severely immunosuppressed patients. This review focuses on manifestations of HZ and its management. Although several articles have been published on HZ, the literature continues to evolve, especially in regard to patients with comorbidities and immunocompromised patients. VZV reactivation has also emerged as an important point of discussion during the COVID-19 pandemic, especially after vaccination. The objective of this review is to discuss current updates related to clinical presentations, complications, and management of HZ.


Assuntos
Gerenciamento Clínico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/patogenicidade , Vacinas contra Herpesvirus/imunologia , Herpes Zoster/complicações , Herpes Zoster/fisiopatologia , Vacinas contra Herpesvirus/administração & dosagem , Vacinas contra Herpesvirus/classificação , Humanos , Hospedeiro Imunocomprometido , Incidência , Infecção Latente/virologia , Morbidade , Neuralgia Pós-Herpética/virologia , Fatores de Risco , Vacinação , Vacinas Sintéticas/administração & dosagem
9.
Virology ; 566: 98-105, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896902

RESUMO

The innate and acquired immune response induced by a commercial inactivated vaccine against Bovine Herpesvirus-1 (BoHV-1) and protection conferred against the virus were analyzed in cattle. Vaccination induced high levels of BoHV-1 antibodies at 30, 60, and 90 days post-vaccination (dpv). IgG1 and IgG2 isotypes were detected at 90 dpv, as well as virus-neutralizing antibodies. An increase of anti-BoHV-1 IgG1 in nasal swabs was detected 6 days post-challenge in vaccinated animals. After viral challenge, lower virus excretion and lower clinical score were observed in vaccinated as compared to unvaccinated animals, as well as BoHV-1-specific proliferation of lymphocytes and production of IFNγ, TNFα, and IL-4. Downregulation of the expression of endosome Toll-like receptors 8-9 was detected after booster vaccination. This is the first thorough study of the immunity generated by a commercial vaccine against BoHV-1 in cattle.


Assuntos
Anticorpos Neutralizantes/biossíntese , Herpesvirus Bovino 1/imunologia , Vacinas contra Herpesvirus/administração & dosagem , Imunoglobulina G/biossíntese , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Receptor 8 Toll-Like/imunologia , Receptor Toll-Like 9/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Anticorpos Antivirais , Bovinos , Proliferação de Células , Endossomos/imunologia , Endossomos/metabolismo , Expressão Gênica , Herpesvirus Bovino 1/patogenicidade , Imunidade Inata/efeitos dos fármacos , Imunização Secundária/métodos , Rinotraqueíte Infecciosa Bovina/genética , Rinotraqueíte Infecciosa Bovina/imunologia , Rinotraqueíte Infecciosa Bovina/virologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Linfócitos/imunologia , Linfócitos/virologia , Masculino , Cavidade Nasal/imunologia , Cavidade Nasal/virologia , Receptor 8 Toll-Like/agonistas , Receptor 8 Toll-Like/genética , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Vacinação/métodos , Vacinas de Produtos Inativados
10.
Vet Res ; 52(1): 91, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158102

RESUMO

Understanding the mechanisms of transmission of infectious laryngotracheitis virus (ILTV) is critical to proper control as both vaccine and wild-type strains circulate within chicken flocks with potential adverse consequences. The relative efficiency of transmission by direct contact between chickens and airborne transmission has not been investigated. Furthermore, relatively high levels of ILTV DNA have been detected in poultry dust and blood but the infectivity of these is unknown. In this study, comparison of in-contact and airborne transmission of two vaccine and one field strain of ILTV revealed that all transmitted to 100% of in-contact birds by 6 days post-exposure (dpe). Airborne transmission without contact resulted in 100% transmission by 14 and 17 dpe for the wild-type and Serva vaccine virus but only 27% transmission by 21 dpe for the A20 vaccine virus. The infectivity of dust or extracts of dust and blood or plasma from infected chickens at various stages of infection was assessed by inoculation into susceptible chickens. There was no transmission by any of these materials. In conclusion, direct contact facilitated efficient ILTV transmission but the virus was unable to be transmitted by dust from infected chickens suggestive of a limited role in the epidemiology of ILTV.


Assuntos
Poeira , Infecções por Herpesviridae/veterinária , Herpesvirus Galináceo 1/fisiologia , Vacinas contra Herpesvirus/efeitos adversos , Doenças das Aves Domésticas/transmissão , Animais , Sangue/virologia , Galinhas , Infecções por Herpesviridae/transmissão , Infecções por Herpesviridae/virologia , Abrigo para Animais , Plasma/virologia , Doenças das Aves Domésticas/virologia , Replicação Viral
11.
J Virol ; 95(12)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-33827944

RESUMO

Koi herpesvirus (KHV) is highly contagious and lethal to cyprinid fish, causing significant economic losses to the carp aquaculture industry, particularly to koi carp breeders. Vaccines delivered through intramuscular needle injection or gene gun are not suitable for mass vaccination of carp. So, the development of cost-effective oral vaccines that are easily applicable at a farm level is highly desirable. In this study, we utilized chitosan-alginate capsules as an oral delivery system for a live probiotic (Lactobacillus rhamnosus) vaccine, pYG-KHV-ORF81/LR CIQ249, expressing KHV ORF81 protein. The tolerance of the encapsulated recombinant Lactobacillus to various digestive environments and the ability of the probiotic strain to colonize the intestine of carp was tested. The immunogenicity and the protective efficacy of the encapsulated probiotic vaccine was evaluated by determining IgM levels, lymphocyte proliferation, expression of immune-related genes, and viral challenge to vaccinated fish. It was clear that the chitosan-alginate capsules protected the probiotic vaccine effectively against extreme digestive environments, and a significant level (P < 0.01) of antigen-specific IgM with KHV-neutralizing activity was detected, which provided a protection rate of ca. 85% for koi carp against KHV challenge. The strategy of using chitosan-alginate capsules to deliver probiotic vaccines is easily applicable for mass oral vaccination of fish.IMPORTANCE An oral probiotic vaccine, pYG-KHV-ORF81/LR CIQ249, encapsulated by chitosan-alginate capsules as an oral delivery system was developed for koi carp against koi herpesvirus (KHV) infection. This encapsulated probiotic vaccine can be protected from various digestive environments and maintain effectively high viability, showing a good tolerance to digestive environments. This encapsulated probiotic vaccine has a good immunogenicity in koi carp via oral vaccination, and a significant level of antigen-specific IgM was effectively induced after oral vaccination, displaying effective KHV-neutralizing activity. This encapsulated probiotic vaccine can provide effective protection for koi carp against KHV challenge, which is handling-stress free for the fish, cost effective, and suitable for the mass oral vaccination of koi carp at a farm level, suggesting a promising vaccine strategy for fish.


Assuntos
Carpas , Doenças dos Peixes/prevenção & controle , Infecções por Herpesviridae/veterinária , Herpesviridae/imunologia , Vacinas contra Herpesvirus/administração & dosagem , Probióticos , Proteínas Virais/imunologia , Administração Oral , Alginatos , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Cápsulas , Proliferação de Células , Quitosana , Infecções por Herpesviridae/prevenção & controle , Vacinas contra Herpesvirus/imunologia , Imunogenicidade da Vacina , Imunoglobulina M/sangue , Lacticaseibacillus rhamnosus , Linfócitos/fisiologia , Vacinação em Massa/veterinária , Proteínas Recombinantes de Fusão , Baço/imunologia , Baço/metabolismo , Vacinas Sintéticas/administração & dosagem , Proteínas Virais/genética
13.
Res Vet Sci ; 136: 185-191, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677208

RESUMO

The Bovine herpes virus type 5 glycoprotein D (gD) is essential for viral penetration into host permissive cells. The Herpes virus gD glycoprotein has been used for bovine immunization, being efficient in reduction of viral replication, shedding and clinical signs, however sterilizing immunity is still not achieved. Recombinant subunit vaccines are, in general, poorly immunogenic requiring additional adjuvant components. Interleukin 17A (IL17A) is a pro-inflammatory cytokine produced by T helper 17 cells that mediate mucosal immunity. IL17 production during vaccine-induced immunity is a requirement for mucosal protection to several agents. In this study, we investigated the potential of a recombinant IL17A to act as an adjuvant for a recombinant BoHV-5 glycoprotein D vaccine in cattle. Three cattle groups were divided as: group 1) rgD5 + alumen + rIL-17A; 2) rgD5 + alumen; and 3) PBS + alumen. The cattle (3 per group) received two doses of their respective vaccines at an interval of 21 days. The group that received rIL17 in its vaccine formulation at the 7th day after the prime immunization had significant higher levels of specific rgD-IgG than the alumen group. Addition of rIL17 also led to a significant fold increase in specific anti-rgD IgG and neutralizing antibodies to the virus, respectively, when compared with the alumen group. Cells stimulated with rIL17A responded with IL17 transcription, as well IL2, IL4, IL10, IL15, Bcl6 and CXCR5. Our findings suggest that the rIL17A has adjuvant potential for use in vaccines against BoHV-5 as well as potentially other pathogens of cattle.


Assuntos
Anticorpos Antivirais/imunologia , Doenças dos Bovinos/prevenção & controle , Encefalite Viral/veterinária , Infecções por Herpesviridae/veterinária , Herpesvirus Bovino 5/imunologia , Vacinas contra Herpesvirus/imunologia , Meningoencefalite/veterinária , Adjuvantes Imunológicos , Animais , Anticorpos Neutralizantes/imunologia , Bovinos , Encefalite Viral/prevenção & controle , Infecções por Herpesviridae/prevenção & controle , Herpesvirus Bovino 5/genética , Imunização/veterinária , Interleucina-17/genética , Interleucina-17/imunologia , Meningoencefalite/prevenção & controle , Vacinas Sintéticas , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
14.
Arch Virol ; 166(2): 571-579, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410993

RESUMO

This study compared concurrent and separate primary vaccination against equid alphaherpesviruses 1 and 4, genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and equine influenza A virus, genus Alphainfluenzavirus, family Orthomyxoviridae. Their vernacular names are equine herpesvirus 1 and 4 (EHV1/4) and equine influenza virus (EIV). Infection with these respiratory pathogens is associated with loss of performance, interruption of training schedules, and on occasion, cancellation of equestrian events. Vaccination is highly recommended, and for some activities it is a mandatory requirement of the relevant authority. As there is a dearth of information relating to the impact of concurrent vaccination on the antibody response to EHV and EIV vaccines, they are usually administered separately, often 2 weeks apart. In a previous study of booster vaccination in Thoroughbred racehorses, concurrent vaccination with whole-virus inactivated carbopol-adjuvanted EHV and EIV vaccines did not impact negatively on the antibody response. In this study, investigations were extended to concurrent versus separate primary vaccination of warmblood foals. A field study was conducted to compare the immune response to a carbopol-adjuvanted EHV vaccine and an immune stimulating complex (ISCOM)-adjuvanted EI vaccine administered concurrently and 2 weeks apart. No adverse clinical reactions were observed, the pattern of EI and EHV antibody response was similar for both groups, and there was no evidence that concurrent primary vaccination compromised the humoral response. The results are of relevance to horse owners who wish to decrease veterinary costs, limit handling of young animals, and simplify record keeping by vaccinating concurrently.


Assuntos
Infecções por Herpesviridae/imunologia , Vacinas contra Herpesvirus/imunologia , Doenças dos Cavalos/imunologia , Cavalos/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Feminino , Doenças dos Cavalos/virologia , Cavalos/virologia , Imunidade Humoral/imunologia , Imunização Secundária/métodos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia
15.
Value Health ; 24(1): 41-49, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33431152

RESUMO

OBJECTIVES: Cost-effectiveness analyses (CEA) are based on the value judgment that health outcomes (eg, quantified in quality-adjusted life-years; QALYs) are all equally valuable irrespective of their context. Whereas most published CEAs perform extensive sensitivity analysis on various parameters and assumptions, only rarely is the influence of the QALY-equivalence assumption on cost-effectiveness results investigated. We illustrate how the integration of alternative social value judgments in CEA can be a useful form of sensitivity analysis. METHODS: Because varicella-zoster virus (VZV) vaccination affects 2 distinct diseases (varicella zoster and herpes zoster) and likely redistributes infections across different age groups, the program has an important equity dimension. We used a cost-effectiveness model and disentangled the share of direct protection and herd immunity within the total projected QALYs resulting from a 50-year childhood VZV program in the UK. We use the UK population's preferences for QALYs in the vaccine context to revalue QALYs accordingly. RESULTS: Revaluing different types of QALYs for different age groups in line with public preferences leads to a 98% change in the projected net impact of the program. The QALYs gained among children through direct varicella protection become more important, whereas the QALYs lost indirectly through zoster in adults diminish in value. Weighting of vaccine-related side effects made a large difference. CONCLUSIONS: Our study shows that a sensitivity analysis in which alternative social value judgments about the value of health outcomes are integrated into CEA of vaccines is relatively straightforward and provides important additional information for decision makers to interpret cost-effectiveness results.


Assuntos
Análise Custo-Benefício/métodos , Vacinas contra Herpesvirus/administração & dosagem , Vacinas contra Herpesvirus/economia , Valores Sociais , Infecção pelo Vírus da Varicela-Zoster/prevenção & controle , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comportamento do Consumidor , Técnicas de Apoio para a Decisão , Vacinas contra Herpesvirus/efeitos adversos , Humanos , Imunidade Coletiva , Lactente , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Reino Unido/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/economia , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Adulto Jovem
16.
Transbound Emerg Dis ; 68(2): 587-597, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32643286

RESUMO

New technologies in the field of vaccinology arise as a necessity for the treatment and control of many diseases. Whole virus inactivated vaccines and modified live virus ones used against Bovine Herpesvirus-1 (BoHV-1) infection have several disadvantages. Previous works on DNA vaccines against BoHV-1 have demonstrated the capability to induce humoral and cellular immune responses. Nevertheless, 'naked' DNA induces low immunogenic response. Thus, loading of antigen encoding DNA sequences in liposomal formulations targeting dendritic cell receptors could be a promising strategy to better activate these antigen-presenting cells (APC). In this work, a DNA-based vaccine encoding the truncated version of BoHV-1 glycoprotein D (pCIgD) was evaluated alone and encapsulated in a liposomal formulation containing LPS and decorated with MANα1-2MAN-PEG-DOPE (pCIgD-Man-L). The vaccinations were performed in mice and bovines. The results showed that the use of pCIgD-Man-L enhanced the immune response in both animal models. For humoral immunity, significant differences were achieved when total antibody titres and isotypes were assayed in sera. Regarding cellular immunity, a significant increase in the proliferative response against BoHV-1 was detected in animals vaccinated with pCIgD-Man-L when compared to the response induced in animals vaccinated with pCIgD. In addition, upregulation of CD40 molecules on the surface of bovine dendritic cells (DCs) was observed when cells were stimulated and activated with the vaccine formulations. When viral challenge was performed, bovines vaccinated with MANα1-2MAN-PEG-DOPE elicited better protection which was evidenced by a lower viral excretion. These results demonstrate that the dendritic cell targeting using MANα1-2MAN decorated liposomes can boost the immunogenicity resulting in a long-lasting immunity. Liposomes decorated with MANα1-2MAN-PEG-DOPE were tested for the first time as a DNA vaccine nanovehicle in cattle as a preventive treatment against BoHV-1. These results open new perspectives for the design of vaccines for the control of bovine rhinotracheitis.


Assuntos
Doenças dos Bovinos/prevenção & controle , Infecções por Herpesviridae/veterinária , Herpesvirus Bovino 1/imunologia , Vacinas contra Herpesvirus/administração & dosagem , Vacinação/veterinária , Animais , Bovinos , Infecções por Herpesviridae/prevenção & controle , Masculino , Camundongos , Vacinas de DNA/administração & dosagem
17.
mSphere ; 5(6)2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33361122

RESUMO

High-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV-2) vaccine. First, we observed that in HSV-2-positive cervical intraepithelial neoplasia (CIN) II patients, HIFU treatment induced significantly higher anti-HSV-2 neutralization response than surgical removal. Next, we tested the efficacy of HIFU-treated, UV-inactivated HSV-2-infected cells as a proof-of-concept vaccine in mice. Our data showed that HIFU-treated formulation significantly enhanced HSV-2 antibody titers and neutralization titers, compared to UV-, microwave (MW)-, or freeze-thaw (FT)-treated formulations. HIFU treatment also promoted the Th1/2 cell-mediated response. A long-term full protection was observed in mice that received the HIFU-treated formulation, and no weight loss was detected. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.IMPORTANCE High-intensity focused ultrasound (HIFU) is mainly used in tumor ablation and tumor vaccinology study. It has been shown to induce immune sensitization and enhance tumor responsiveness to other therapies. Our study has shown enhanced anti-HSV-2 response in HIFU-treated CIN II patients. Furthermore, in a murine model, we have demonstrated that HIFU-treated HSV-2 vaccine induced long-term protective immunity against lethal challenge. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Herpes Simples/prevenção & controle , Herpesvirus Humano 2/imunologia , Vacinas contra Herpesvirus/imunologia , Ultrassom Focalizado Transretal de Alta Intensidade/métodos , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Chlorocebus aethiops , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Herpes Simples/imunologia , Herpes Simples/virologia , Herpesvirus Humano 2/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Células Th1/imunologia , Células Th2/imunologia , Células Vero
18.
PLoS Pathog ; 16(7): e1008795, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32716975

RESUMO

HSV-1 causes 50% of first-time genital herpes infections in resource-rich countries and affects 190 million people worldwide. A prophylactic herpes vaccine is needed to protect against genital infections by both HSV-1 and HSV-2. Previously our laboratory developed a trivalent vaccine that targets glycoproteins C, D, and E present on the HSV-2 virion. We reported that this vaccine protects animals from genital disease and recurrent virus shedding following lethal HSV-2 challenge. Importantly the vaccine also generates cross-reactive antibodies that neutralize HSV-1, suggesting it may provide protection against HSV-1 infection. Here we compared the efficacy of this vaccine delivered as protein or nucleoside-modified mRNA immunogens against vaginal HSV-1 infection in mice. Both the protein and mRNA vaccines protected mice from HSV-1 disease; however, the mRNA vaccine provided better protection as measured by lower vaginal virus titers post-infection. In a second experiment, we compared protection provided by the mRNA vaccine against intravaginal challenge with HSV-1 or HSV-2. Vaccinated mice were totally protected against death, genital disease and infection of dorsal root ganglia caused by both viruses, but somewhat better protected against vaginal titers after HSV-2 infection. Overall, in the two experiments, the mRNA vaccine prevented death and genital disease in 54/54 (100%) mice infected with HSV-1 and 20/20 (100%) with HSV-2, and prevented HSV DNA from reaching the dorsal root ganglia, the site of virus latency, in 29/30 (97%) mice infected with HSV-1 and 10/10 (100%) with HSV-2. We consider the HSV-2 trivalent mRNA vaccine to be a promising candidate for clinical trials for prevention of both HSV-1 and HSV-2 genital herpes.


Assuntos
Proteção Cruzada/imunologia , Herpes Genital , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Vacinas contra Herpesvirus/imunologia , Latência Viral/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Feminino , Herpes Genital/virologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro , Proteínas do Envelope Viral/imunologia
19.
PLoS Pathog ; 16(7): e1008609, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32702057

RESUMO

Primary infection of human herpesvirus 6B (HHV-6B) occurs in infants after the decline of maternal immunity and causes exanthema subitum accompanied by a high fever, and it occasionally develops into encephalitis resulting in neurological sequelae. There is no effective prophylaxis for HHV-6B, and its development is urgently needed. The glycoprotein complex gH/gL/gQ1/gQ2 (called 'tetramer of HHV-6B') on the virion surface is a viral ligand for its cellular receptor human CD134, and their interaction is thus essential for virus entry into the cells. Herein we examined the potency of the tetramer as a vaccine candidate against HHV-6B. We designed a soluble form of the tetramer by replacing the transmembrane domain of gH with a cleavable tag, and the tetramer was expressed by a mammalian cell expression system. The expressed recombinant tetramer is capable of binding to hCD134. The tetramer was purified to homogeneity and then administered to mice with aluminum hydrogel adjuvant and/or CpG oligodeoxynucleotide adjuvant. After several immunizations, humoral and cellular immunity for HHV-6B was induced in the mice. These results suggest that the tetramer together with an adjuvant could be a promising candidate HHV-6B vaccine.


Assuntos
Exantema Súbito/imunologia , Vacinas contra Herpesvirus/imunologia , Proteínas do Envelope Viral/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Exantema Súbito/virologia , Herpesvirus Humano 6 , Humanos , Camundongos , Camundongos Endogâmicos BALB C
20.
Cell Mol Life Sci ; 77(21): 4315-4324, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32367191

RESUMO

Epstein-Barr virus (EBV) was the first human tumor virus being discovered and remains to date the only human pathogen that can transform cells in vitro. 55 years of EBV research have now brought us to the brink of an EBV vaccine. For this purpose, recombinant viral vectors and their heterologous prime-boost vaccinations, EBV-derived virus-like particles and viral envelope glycoprotein formulations are explored and are discussed in this review. Even so, cell-mediated immune control by cytotoxic lymphocytes protects healthy virus carriers from EBV-associated malignancies, antibodies might be able to prevent symptomatic primary infection, the most likely EBV-associated pathology against which EBV vaccines will be initially tested. Thus, the variety of EBV vaccines reflects the sophisticated life cycle of this human tumor virus and only vaccination in humans will finally be able to reveal the efficacy of these candidates. Nevertheless, the recently renewed efforts to develop an EBV vaccine and the long history of safe adoptive T cell transfer to treat EBV-associated malignancies suggest that this oncogenic γ-herpesvirus can be targeted by immunotherapies. Such vaccination should ideally implement the very same immune control that protects healthy EBV carriers.


Assuntos
Infecções por Vírus Epstein-Barr/prevenção & controle , Herpesvirus Humano 4/imunologia , Vacinas contra Herpesvirus/uso terapêutico , Animais , Anticorpos Neutralizantes/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Vacinas contra Herpesvirus/imunologia , Humanos , Vacinação , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/uso terapêutico , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/uso terapêutico
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