RESUMO
BACKGROUND: Protection against herpes zoster is primarily conferred by cell-mediated immunity. However, anti-varicella-zoster virus (VZV) glycoprotein (anti-gp) antibody responses to zoster vaccine live (ZVL) are correlated with protection, suggesting a potential protective role for antibody. Detailed studies of antibody responses to the recombinant zoster vaccine (RZV) are provided. METHODS: We compared enzyme-linked immunosorbent assay-measured anti-VZV glycoproteins (anti-gp) and glycoprotein E (anti-gE) antibody levels and avidity in 159 participants randomized to RZV (n = 80) or ZVL (n = 79) recipients over 5 years after vaccination and identified predictors of antibody persistence. RESULTS: The comparison between vaccine groups showed higher anti-gE and anti-gp antibody levels after RZV than after ZVL over the 5-year study duration. RZV recipients also had higher anti-gE avidity for 5 years and higher anti-gp avidity in the first year after vaccination. Compared with prevaccination levels, RZV recipients maintained higher levels of anti-gE antibodies and avidity for 5 years, whereas ZVL recipients only maintained higher anti-gE avidity. Anti-gp antibody levels and avidity decreased to prevaccination levels or below beyond 1 year after vaccination in both groups. Independent predictors of persistence of antibody levels and avidity included vaccine type, prevaccination and peak antibody levels and avidity, prevaccination and peak cell-mediated immunity, and age. Sex or prior ZVL administration did not affect persistence. CONCLUSIONS: Antibody responses and avidity were higher and more persistent in RZV than in ZVL recipients. The effect of age on antibody persistence in RZV recipients is novel.
Assuntos
Vacina contra Herpes Zoster , Herpes Zoster , Humanos , Formação de Anticorpos , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Glicoproteínas , Vacinas SintéticasRESUMO
Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.
Assuntos
Exantema , Herpes Zoster , Humanos , Herpesvirus Humano 3 , Pele , DNA Viral/genéticaRESUMO
Background and Purpose: A large proportion of ischemic stroke patients lack a definitive stroke etiology despite extensive diagnostic testing. Varicella-Zoster Virus (VZV) can directly invade blood vessels causing vasculitis and may be associated with cryptogenic stroke (CS). Methods: We conducted a retrospective cross-sectional study of CS patients tested for VZV. The following were considered evidence of VZV reactivation (VZV+): positive CSF VZV PCR, anti-VZV IgM in CSF, or anti-VZV IgG CSF/serum ratio of 1:10 or higher. We describe the cohort, report VZV+ proportion with 95% confidence intervals (CI) determined with the Wald method, and compare patient groups using standard statistical tests. Results: A total of 72 CS patients met full study inclusion criteria. Most of the patients were <65 years old, had few traditional vascular risk factors, and had multifocal infarcts. Mean age was 49 years (SD ±13) and 47% were women. A total of 14 patients (19.4%; CI: 11.4-30.8%) had evidence of CNS VZV reactivation. There was no difference in evaluated demographic or radiographic features between those with versus without evidence of VZV reactivation. History of ischemic stroke in the past year (11/14 vs 25/43, P<.05) and hypertension (13/14 vs 35/58 and P<.05) were associated with VZV+. Conclusion: We found a high proportion of CNS VZV reactivation in a cross-sectional cohort of CS patients selected for CSF testing. Testing for VZV might be reasonable in CS patients who are young, have multifocal infarcts, or had an ischemic stroke within the past year, but additional research is needed.
RESUMO
Monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B-cell disorders associated with an increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by 2 months. Responses assessed at 3 and 12 months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color Interferon-γ and Interleukin-2FLUOROSPOT assays were compared to historic controls matched by age and sex. About 62 patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, p = .03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs. 36%, respectively, p = .23). The CD4+ T-cell response to vaccination was significantly lower in study participants compared to controls (54% vs. 96%, p < .001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs. 73%, p = .008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n = 47), 24% had antibody titers below the response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T-cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed.
Assuntos
Vacina contra Herpes Zoster/uso terapêutico , Herpes Zoster/prevenção & controle , Imunidade Celular , Imunidade Humoral , Leucemia Linfocítica Crônica de Células B/complicações , Linfocitose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Herpes Zoster/imunologia , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Linfocitose/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): (i) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV) and (ii) recombinant adjuvanted vaccine (RZV) containing recombinant varicella-zoster virus (VZV) glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, is considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination (19 and 12 avidity index units [AIU], respectively). RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost, 47 AIU versus 22 AIU; mean neutralizing antibody boost, 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r = 0.5) and moderately with gp avidity increases (r = 0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses.IMPORTANCE These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity and neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development will benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials.
Assuntos
Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacina contra Herpes Zoster/imunologia , Herpesvirus Humano 3/imunologia , Adjuvantes Imunológicos , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Afinidade de Anticorpos , Ensaio de Imunoadsorção Enzimática , Herpes Zoster/prevenção & controle , Humanos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Vacinas Atenuadas/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/imunologiaRESUMO
BACKGROUND: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes. CONCLUSIONS: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.
Assuntos
Vacina contra Herpes Zoster/administração & dosagem , Herpesvirus Humano 3/imunologia , Imunogenicidade da Vacina , Transplante de Órgãos , Infecção pelo Vírus da Varicela-Zoster/prevenção & controle , Adulto , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Feminino , Vacina contra Herpes Zoster/efeitos adversos , Herpesvirus Humano 3/patogenicidade , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunização , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Estudo de Prova de Conceito , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/virologia , Proteínas do Envelope Viral/imunologiaRESUMO
Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 106 CD4+ T cells; IQR: 46-180) to the first (median 128 per 106 CD4+ T cells; IQR: 82-353; p = .023) and after the second dose (median 361 per 106 CD4+ T cells; IQR: 146-848; p < .0001). Tenderness (83.0%; 95%CI: 69.2-92.4%) and redness (31.9%; 95%CI: 19.1-47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.
Assuntos
Vacina contra Herpes Zoster , Herpes Zoster , Anticorpos Antivirais , Vacina contra Herpes Zoster/efeitos adversos , Humanos , Pulmão , TransplantadosRESUMO
Known human coronaviruses (hCoV) usually cause mild to moderate upper-respiratory tract illnesses, except SARS-CoV and MERS-CoV, which, in addition to mild illness can also be associated with severe respiratory diseases and high mortality rates. Well-characterized multiplexed serologic assays are needed to aid in rapid detection and surveillance of hCoVs. The present study describes development and evaluation of a multiplexed magnetic microsphere immunoassay (MMIA) to simultaneously detect immunoglobulin G (IgG) antibodies specific for recombinant nucleocapsid proteins (recN) from hCoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV. We used paired human sera to screen for IgG with reactivity against six hCoVs to determine assay sensitivity, specificity and reproducibility. We found no signal interference between monoplex and multiplex assay formats (R2 range = 0.87-0.97). Screening of paired human sera using MMIA, resulted in 92 of 106 (sensitivity: 86%) as positive and 68 of 80 (specificity: 84%) as negative. This study serves as a proof of concept that it is feasible to develop and use a multiplexed microsphere immunoassay as a next generation screening tool for use in large scale seroprevalence studies of hCoVs.
Assuntos
Anticorpos Antivirais/sangue , Coronavirus/imunologia , Imunoensaio/métodos , Imunoglobulina G/sangue , Antígenos Virais/imunologia , Reações Cruzadas/imunologia , Fluorescência , Humanos , Microesferas , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Background: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. Methods: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between 1 January 2013 and 9 May 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein enzyme-linked immunosorbent assay and indirect immunofluorescence, with results confirmed by microneutralization assay. Results: Thirty-one of 34 (91%) case patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) case patients with available sera, including 1 severely symptomatic, 9 mildly symptomatic, and 3 asymptomatic case patients. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. Conclusions: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission.
Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecções por Coronavirus/imunologia , Ensaio de Imunoadsorção Enzimática , Saúde da Família , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Emirados Árabes Unidos/epidemiologia , Adulto JovemRESUMO
RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab). In this study, we have tested two human anti-RSV G mAbs, 2B11 and 3D3, by both prophylactic and therapeutic treatment for RSV in the BALB/c mouse model. Both anti-G mAbs reduced viral load, leukocyte infiltration and IFN-γ and IL-4 expression in cell-free BAL supernatants emphasizing the potential of anti-G mAbs as anti-inflammatory and antiviral strategies.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Pneumonia/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Antivirais/uso terapêutico , Modelos Animais de Doenças , Feminino , Pulmão/efeitos dos fármacos , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/prevenção & controle , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Organismos Livres de Patógenos Específicos , Carga ViralRESUMO
The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or microneutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.
Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes Sorológicos/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Algoritmos , HumanosRESUMO
In 2014, the Centers for Disease Control and Prevention conducted conveyance contact investigations for 2 Middle East respiratory syndrome cases imported into the United States, comprising all passengers and crew on 4 international and domestic flights and 1 bus. Of 655 contacts, 78% were interviewed; 33% had serologic testing. No secondary cases were identified.
Assuntos
Busca de Comunicante , Infecções por Coronavirus/diagnóstico , Controle de Infecções , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , RNA Viral/genética , Adulto , Idoso , Aviação , Centers for Disease Control and Prevention, U.S. , Infecções por Coronavirus/transmissão , Humanos , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Arábia Saudita , Viagem , Estados UnidosRESUMO
To determine how long antibodies against Middle East respiratory syndrome coronavirus persist, we measured long-term antibody responses among persons serologically positive or indeterminate after a 2012 outbreak in Jordan. Antibodies, including neutralizing antibodies, were detectable in 6 (86%) of 7 persons for at least 34 months after the outbreak.
Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Feminino , Humanos , Jordânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014-January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices.
Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Surtos de Doenças , Feminino , Pessoal de Saúde , Humanos , Controle de Infecções/métodos , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Arábia Saudita/epidemiologia , Adulto JovemRESUMO
To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. None of the 48 contacts showed evidence of MERS-CoV infection.
Assuntos
Infecções por Coronavirus/transmissão , Infecção Hospitalar , Pessoal de Saúde , Coronavírus da Síndrome Respiratória do Oriente Médio , Adulto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient's respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. Sequences clustered with those from Saudi Arabia and United Arab Emirates.
Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/microbiologia , Família , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Adulto , Idoso , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Evolução Fatal , Feminino , Genes Virais , Humanos , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Filogenia , Análise de Sequência de DNA , Sorotipagem , Resultado do Tratamento , Tunísia/epidemiologiaRESUMO
Respiratory syncytial virus (RSV) is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV) vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study.
Assuntos
Anticorpos Antivirais/sangue , Peptídeos/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sinciciais Respiratórios/imunologia , Proteínas Virais de Fusão/imunologia , Sequência de Aminoácidos , Animais , Formaldeído , Imunização , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Peptídeos/administração & dosagem , Peptídeos/química , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vírus Sinciciais Respiratórios/química , Vacinas de Produtos Inativados , Proteínas Virais de Fusão/químicaRESUMO
Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory illness in infants and young children worldwide, making it a high priority for development of strategies for prevention and treatment. RSV can cause repeat infections throughout life, with serious complications in elderly and immunocompromised patients. Previous studies indicate that the RSV G protein binds through a CX3C chemokine motif to the host chemokine receptor, CX3CR1, and modulates the inflammatory immune response. In the current study, we examined the contribution of CX3CR1 to the immune response to RSV infection in mice. CX3CR1-deficient mice showed an impaired innate immune response to RSV infection, characterized by substantially decreased NK1.1(+) natural killer, CD11b(+), and RB6-8C5(+) polymorphonuclear cell trafficking to the lung and reduced IFNγ production compared with those in wildtype control mice. Leukocytes from CX3CR1-deficient mice were poorly chemotactic toward RSV G protein and CX3CL1. These results substantiate the importance of the RSV G CX3C-CX3CR1 interaction in the innate immune response to RSV infection.
Assuntos
Imunidade Inata/genética , Receptores de Quimiocinas/deficiência , Infecções por Vírus Respiratório Sincicial/imunologia , Animais , Receptor 1 de Quimiocina CX3C , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Fluorescência Verde/genética , Células Matadoras Naturais/imunologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Quimiocinas/genética , Infecções por Vírus Respiratório Sincicial/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas do Envelope Viral/imunologiaRESUMO
Human coronaviruses are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that require hospitalization. In this study, an assay for one of the human coronaviruses, OC43, was developed using a truncated recombinant nucleocapsid (N) protein antigen in an enzyme immunosorbent assay (ELISA) and evaluated using serum collected from HCoV-OC43-infected patients, healthy adults, and patients with other respiratory virus infections. Results showed that the diagnostic sensitivity and specificity of the assay were 90.9% (10/11) and 82.9% (39/47), respectively. To evaluate the clinical utility of the ELISA, serum samples collected from patients during an outbreak of HCoV-OC43 infection and previously identified as positive by HCoV-OC43 whole N ELISA were screened resulting in 100% diagnosis agreement between the testing methods. These results suggest that this assay offers a reliable method to detect HCoV-OC43 infection and may be a useful tool in coronavirus seroepidemiological studies.
Assuntos
Anticorpos Antivirais/sangue , Coronavirus Humano OC43/imunologia , Ensaio de Imunoadsorção Enzimática , Proteínas do Nucleocapsídeo/imunologia , Animais , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Coronavirus Humano OC43/genética , Reações Cruzadas/imunologia , Humanos , Camundongos , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/isolamento & purificação , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Valores de Referência , Homologia de Sequência de Aminoácidos , Estudos SoroepidemiológicosRESUMO
We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab')(2) forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.