BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2

A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD down, one-RBD up state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFN{gamma}+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates

To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD up, two-RBD down state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFN{gamma}+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (NCT04368728).

Description of Referrals for Colposcopy in a Hospital in Brazil.

OBJECTIVE: To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. METHODS: A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. RESULTS: Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults < 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. CONCLUSION: Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.

OBJETIVO: Descrever os encaminhamentos para colposcopia em um hospital no Brasil e a frequência relativa dos pacientes que foram beneficiados, considerando as indicações corretas para o exame e seus diagnósticos finais. MéTODOS: Foi realizado um estudo retrospectivo no banco de dados do serviço de colposcopia do Hospital Universitário de Taubaté, Taubaté, SP, Brasil. A frequência validou em análise de prontuários de mulheres encaminhadas por indicação clínica ou alteração citológica, atendidas no período de março de 2015 a março de 2017. A população selecionada e analisada incluiu 256 resultados que estavam correlacionadas aos dados citológicos, clínicos e com o resultado da colposcopia. RESULTADOS: Das mulheres encaminhadas, 45% apresentaram-se fora da idade de rastreamento conforme as diretrizes de rastreio de câncer de colo uterino, sendo que 8,6% eram adolescentes e adultas jovens < 25 anos de idade e 36,4% das pacientes tinham idade ≥ 65 anos. Um total de 50% das pacientes não possuía indicação de colposcopia, ou seja, citologias normais, de alterações benignas, ectopia, cervicite, células escamosas atípicas de significado indeterminado (ASC-US) e lesão intraepitelial escamosa de baixo grau (LSIL) sem persistência e aspecto clínico normal. Um total de 39,84% das pacientes que realizaram a colposcopia tiveram resultados de lesão de alto grau ou câncer e, dessa forma, se beneficiaram com o encaminhamento adequado. CONCLUSãO: A maioria (60,16%) das pacientes encaminhadas para o serviço de colposcopia não se beneficiou com o encaminhamento, por resultados sem alterações como colposcopias negativas, histologias com ausência de neoplasia intraepitelial cervical (NIC) ou apenas NIC 1, ou estavam fora da idade de rastreamento. Esses achados demonstram, portanto, significativo número de encaminhamentos desnecessários e inadequados.

Description of referrals for colposcopy in a hospital in Brazil / Descrição dos encaminhamentos para colposcopia em um hospital no Brasil

Abstract Objective To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. Methods A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. Results Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults < 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. Conclusion Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.

Resumo Objetivo Descrever os encaminhamentos para colposcopia em um hospital no Brasil e a frequência relativa dos pacientes que foram beneficiados, considerando as indicações corretas para o exame e seus diagnósticos finais. Métodos Foi realizado um estudo retrospectivo no banco de dados do serviço de colposcopia do Hospital Universitário de Taubaté, Taubaté, SP, Brasil. A frequência validou em análise de prontuários de mulheres encaminhadas por indicação clínica ou alteração citológica, atendidas no período de março de 2015 a março de 2017. A população selecionada e analisada incluiu 256 resultados que estavam correlacionadas aos dados citológicos, clínicos e com o resultado da colposcopia. Resultados Das mulheres encaminhadas, 45% apresentaram-se fora da idade de rastreamento conforme as diretrizes de rastreio de câncer de colo uterino, sendo que 8,6% eram adolescentes e adultas jovens < 25 anos de idade e 36,4% das pacientes tinham idade ≥ 65 anos. Um total de 50% das pacientes não possuía indicação de colposcopia, ou seja, citologias normais, de alterações benignas, ectopia, cervicite, células escamosas atípicas de significado indeterminado (ASC-US) e lesão intraepitelial escamosa de baixo grau (LSIL) sem persistência e aspecto clínico normal. Um total de 39,84% das pacientes que realizaram a colposcopia tiveram resultados de lesão de alto grau ou câncer e, dessa forma, se beneficiaram com o encaminhamento adequado. Conclusão A maioria (60,16%) das pacientes encaminhadas para o serviço de colposcopia não se beneficiou com o encaminhamento, por resultados sem alterações como colposcopias negativas, histologias com ausência de neoplasia intraepitelial cervical (NIC) ou apenas NIC 1, ou estavam fora da idade de rastreamento. Esses achados demonstram, portanto, significativo número de encaminhamentos desnecessários e inadequados.