RESUMO
OBJECTIVES: The capability of the SARS-CoV-2 Omicron variant to escape immunity conferred by mRNA vaccines has led to the development of Omicron-adapted vaccines. In this study, we aimed to compare the immune response with the ancestral strain and with the BA.1 Omicron variant after administration of the original vaccine and the Omicron-adapted vaccine. METHODS: This is an ongoing phase 3, double-blinded randomized controlled trial, comparing the original BNT161b2 vaccine, monovalent Omicron BA.1-adapted BNT161b2 vaccine, and bivalent combinations. Each vaccine was given at a 30 µg and 60 µg dose. Primary outcomes considered included neutralization titers of SARS-CoV-2 ancestral strain and Omicron BA.1. Exploratory endpoints included neutralization titers for Omicron BA.5, and the incidence of COVID-19 cases. RESULTS: Overall, 122 individuals (22, 19, 20, 20, 20, 20, and 21 in each arm) completed a 90-day follow-up. Three months after vaccination, adjusting for baseline levels, neutralizing antibody titers were 0.63 (95% CI: 0.3-1.32) and 0.54 (0.24-1.2) for monovalent/60 µg, 0.9 (0.42-1.92) and 2.69 (1.17-6.17) times for monovalent-Omi.BA.1/30 µg, 1.28 (0.6-2.75) and 2.79 (1.21-6.41) times for monovalent-Omi.BA.1/60 µg, 0.96 (0.46-1.97) and 2.07 (0.93-4.58) times for bivalent-Omi.BA.1/30 µg, and 0.79 (0.38-1.63) and 1.95 (0.88-4.32) times for bivalent-Omi.BA.1/60 µg when compared with BNT162b2/30 µg against the ancestral strain and BA.1 variant, respectively. DISCUSSION: BA.1-adapted mRNA vaccines lead to a stronger neutralizing antibody response against the Omicron BA.1 sub-variant.
Assuntos
COVID-19 , Vacinas , Humanos , Vacina BNT162 , Seguimentos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vacinas de mRNA , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
BACKGROUND: Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19. METHODS: In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data. FINDINGS: From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30). INTERPRETATION: Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses. FUNDING: Israeli Ministry of Health.
Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Israel/epidemiologia , Vacina BNT162 , Estudos Prospectivos , Anticorpos Neutralizantes , Imunoglobulina GRESUMO
Zika virus (ZIKV) infection during pregnancy may cause severe fetal abnormalities and therefore it is important to diagnose and distinguish between recent and past Zika infection. Serological diagnosis assays detect antibodies against the envelope protein, that suffer from high cross-reactivity. In addition, reports regarding long IgM persistence prevent its use in diagnosis of recent Zika infection. Following the Zika pandemic, a novel ELISA assay based on detection of antibodies against Zika nonstructural 1 (NS1) protein was developed (NS1-IgM). Here, NS1-IgM antibodies were assessed in Israeli travelers diagnosed with Zika. NS1-IgM and NS1-IgG antibodies from 36 travelers diagnosed with ZIKV infection were detected as early as 5 days after symptom onset. However, while IgG levels were maintained for several months, IgM levels in all samples declined rapidly and by 31 days after symptom onset, no IgM positive samples were detected. Interval-censored survival analysis demonstrated 25%, 50%, and 75% decline in NS1-IgM levels in 29 days (95% CI: 22-34), 34 days (95% CI: 29-44), and 44 days (95% CI: 34-65), respectively. Our results suggest that IgM antibodies against ZIKV NS1 are short lived and can be used as a reliable marker for diagnosis of recent ZIKV infection.
RESUMO
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.
Assuntos
Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , Surtos de Doenças , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Fatores Etários , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , Criança , Pré-Escolar , Surtos de Doenças/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Coletiva/imunologia , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Características de Residência/estatística & dados numéricos , Estudos Soroepidemiológicos , Fatores de Tempo , Adulto JovemRESUMO
The COVID-19 pandemic and the fast global spread of the disease resulted in unprecedented decline in world trade and travel. A critical priority is, therefore, to quickly develop serological diagnostic capacity and identify individuals with past exposure to SARS-CoV-2. In this study serum samples obtained from 309 persons infected by SARS-CoV-2 and 324 of healthy, uninfected individuals as well as serum from 7 COVID-19 patients with 4-7 samples each ranging between 1-92 days post first positive PCR were tested by an "in house" ELISA which detects IgM, IgA and IgG antibodies against the receptor binding domain (RBD) of SARS-CoV-2. Sensitivity of 47%, 80% and 88% and specificity of 100%, 98% and 98% in detection of IgM, IgA and IgG antibodies, respectively, were observed. IgG antibody levels against the RBD were demonstrated to be up regulated between 1-7 days after COVID-19 detection, earlier than both IgM and IgA antibodies. Study of the antibody kinetics of seven COVID 19 patients revealed that while IgG levels are high and maintained for at least 3 months, IgM and IgA levels decline after a 35-50 days following infection. Altogether, these results highlight the usefulness of the RBD based ELISA, which is both easy and cheap to prepare, to identify COVID-19 patients even at the acute phase. Most importantly our results demonstrate that measuring IgG levels alone is both sufficient and necessary to diagnose past exposure to SARS-CoV-2.
Assuntos
Anticorpos Antivirais/imunologia , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , Imunoglobulina G/imunologia , Pandemias , Domínios Proteicos/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/virologia , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e Especificidade , Adulto JovemRESUMO
Sindbis virus (SINV) is a mosquito-borne alphavirus circulating globally. SINV outbreaks have been mainly reported in North-European countries. In Israel, SINV was detected in 6.3% of mosquito pools; however, SINV infection in humans has rarely been diagnosed. A serologic survey to detect SINV IgG antibodies was conducted to evaluate the seroprevalence of SINV in the Israeli population. In total, 3145 serum samples collected in 2011-2014, representing all age and population groups in Israel, were assessed using an indirect ELISA assay, and a neutralization assay was performed on all ELISA-positive samples. The prevalence rates of SINV IgG antibodies were calculated. Logistic regressions models were applied to assess the association between demographic characteristics and SINV seropositivity. Overall, 113 (3.6%) and 59 (1.9%) samples were positive for ELISA and neutralization SINV IgG, respectively. Multivariable analysis demonstrated that SINV seropositivity was significantly associated with older age and residence outside metropolitan areas. These results demonstrate that, despite no outbreaks or clinical presentation, SINV infects the human population in Israel. Seropositivity is countrywide, more frequent in people of older age, and less diffuse in Israel's metropolitan areas. Seroprevalence studies from other countries will add to our understanding of the global burden of SINV and the risk for potential SINV outbreaks.
Assuntos
Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/virologia , Anticorpos Antivirais/sangue , Sindbis virus/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Neutralizantes , Criança , Pré-Escolar , Estudos Transversais , Culicidae/virologia , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Israel/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Serological diagnosis of Zika virus is challenging due to high cross-reactivity of Zika virus with other flavivirus antibodies. Recently, a Zika NS1-based enzyme-linked immunosorbent assay (ELISA) was developed and shown to be highly specific for Zika antibody detection; however, sensitivity was evaluated for only a small number of confirmed Zika-infected patients. In this study, we measured the sensitivity and kinetics of Zika IgM and IgG antibodies using the Zika NS1-based ELISA in 105 samples from 63 returning travelers infected with Zika virus (proven by PCR or neutralization assay) from Israel, Czech Republic, Italy, Belgium, Germany, and Chile. Zika virus IgM was detected from 2 to 42 days post-symptom onset (PSO) with an overall sensitivity of 79% in the first month and 68% until 2 months PSO, while IgG antibodies were detected from 5 days to 3 years PSO with 79% sensitivity. Interestingly, significant differences in IgM sensitivity and IgM detection period were observed between Israeli and European/Chilean Zika-infected travelers, adding to the complexity of Zika infection diagnosis and suggesting that other diagnostic methods should be complemented to reduce false-negative results.
Assuntos
Anticorpos Antivirais/sangue , Doenças Transmissíveis Importadas/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Testes Sorológicos/métodos , Proteínas não Estruturais Virais/imunologia , Infecção por Zika virus/diagnóstico , Adolescente , Adulto , Idoso , Formação de Anticorpos , Criança , Pré-Escolar , Chile , Europa (Continente) , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo , Viagem , Adulto JovemAssuntos
Doenças Transmissíveis Importadas/transmissão , Doenças Transmissíveis Importadas/virologia , Viagem , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Zika virus , Doenças Transmissíveis Importadas/epidemiologia , Humanos , Israel , Tipagem Molecular , Filogenia , RNA Viral , Sorotipagem , Vietnã , Zika virus/classificação , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/epidemiologiaRESUMO
The current diagnosis of West Nile virus (WNV) infection is primarily based on serology, since molecular identification of WNV RNA is unreliable due to the short viremia and absence of detectable virus in cerebrospinal fluid (CSF). Recent studies have shown that WNV RNA can be detected in urine for a longer period and at higher concentrations than in plasma. In this study, we examined the presence of WNV RNA in serum, plasma, whole-blood, CSF, and urine samples obtained from patients diagnosed with acute WNV infection during an outbreak which occurred in Israel in 2015. Our results demonstrate that 33 of 38 WNV patients had detectable WNV RNA in whole blood at the time of diagnosis, a higher rate than in any of the other sample types tested. Overall, whole blood was superior to all other samples, with 86.8% sensitivity, 100% specificity, 100% positive predictive value, and 83.9% negative predictive value. Interestingly, WNV viral load in urine was higher than in whole blood, CSF, serum, and plasma despite the lower sensitivity than that of whole blood. This study establishes the utility of whole blood in the routine diagnosis of acute WNV infection and suggests that it may provide the highest sensitivity for WNV RNA detection in suspected cases.
Assuntos
Sangue/virologia , Técnicas de Diagnóstico Molecular/métodos , RNA Viral/isolamento & purificação , Manejo de Espécimes/métodos , Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/isolamento & purificação , Líquido Cefalorraquidiano/virologia , Humanos , Israel , Valor Preditivo dos Testes , RNA Viral/genética , Sensibilidade e Especificidade , Urina/virologia , Vírus do Nilo Ocidental/genéticaRESUMO
West Nile Virus (WNV) is endemic in Israel and has been the cause of several outbreaks in recent years. In 2000, a countrywide mosquito survey was established to monitor WNV activity and characterize viral genotypes in Israel. We analyzed data from 7135 pools containing 277 186 mosquitoes collected over the past 15 years and, here, report partial sequences of WNV genomes obtained from 102 of the 336 positive mosquito pools. Phylogenetic analysis demonstrated that cluster 4 and the Mediterranean and Eastern European subtypes of cluster 2 within WNV lineage 1 circulated in Israel, as did WNV lineage 2, highlighting a high genetic diversity of WNV genotypes in our region. As a major crossroads for bird migration between Africa and Eurasia and with a long history of human infection, Israel serves as a resource hub for WNV in Africa and Eurasia and provides valuable information on WNV circulation in these regions.