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Introduction: Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. Methods: We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer). Results: While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19. Discussion: As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.
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COVID-19 , SARS-CoV-2 , Humanos , Olfato , Inmunoglobulina A , Vacunas contra la COVID-19 , Hospitales de EnseñanzaRESUMEN
The development of new vaccines has traditionally been a long-term job, although recent experience with the emergence of Covid-19 has caused development and production delays to skyrocket. The fact remains that the development of vaccines in the preclinical phases and in phases 1 and 2 of clinical development is based on the study of the specific immune response of the adaptive immune system.
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BACKGROUND: We report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CASE: One patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had a similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. DISCUSSION AND CONCLUSION: Thus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , Inmunoglobulina G/sangre , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , SARS-CoV-2/inmunología , Adulto , Anticuerpos Neutralizantes/biosíntesis , COVID-19/transmisión , Infección Hospitalaria/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/biosíntesis , Masculino , Persona de Mediana Edad , Nasofaringe/virología , SARS-CoV-2/clasificación , SARS-CoV-2/genéticaRESUMEN
Three autochthonous cases of Zika virus occurred in southern France in August 2019. Diagnosis relied on serology and transcription-mediated amplification. Attempts for virus isolation and ZIKV genome RT-PCR detection remained negative. Since the index case was not identified, we addressed the issue of genotyping and geographical origin by performing hemi-nested PCR and sequencing in the Pr gene. Analysis of 16 genotype-specific Single Nucleotides Polymorphisms identified the Asian genotype and suggested a Southeast Asia origin.
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Genes Virales/genética , Genotipo , Virus Zika/genética , Virus Zika/aislamiento & purificación , Aedes/virología , Animales , Asia , Transmisión de Enfermedad Infecciosa , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mosquitos Vectores/virología , Polimorfismo de Nucleótido Simple , Infección por el Virus Zika/virologíaRESUMEN
BACKGROUND: Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. METHODS: We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIII-induced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIII-specific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. RESULTS: Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a ZEDIII-based ELISA. Moreover, purified human IgG against D2EDIII or D4EDIII did not bind to ZEDIII and we observed no D4EDIII reactivity with ZIKV-induced mouse polyclonal IgGs. CONCLUSIONS: We developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.