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1.
Sci Transl Med ; 11(501)2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316007

RESUMO

Previous studies have established that strain 68-1-derived rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) proteins (RhCMV/SIV) are able to elicit and maintain cellular immune responses that provide protection against mucosal challenge of highly pathogenic SIV in rhesus monkeys (RMs). However, these efficacious RhCMV/SIV vectors were replication and spread competent and therefore have the potential to cause disease in immunocompromised subjects. To develop a safer CMV-based vaccine for clinical use, we attenuated 68-1 RhCMV/SIV vectors by deletion of the Rh110 gene encoding the pp71 tegument protein (ΔRh110), allowing for suppression of lytic gene expression. ΔRh110 RhCMV/SIV vectors are highly spread deficient in vivo (~1000-fold compared to the parent vector) yet are still able to superinfect RhCMV+ RMs and generate high-frequency effector-memory-biased T cell responses. Here, we demonstrate that ΔRh110 68-1 RhCMV/SIV-expressing homologous or heterologous SIV antigens are highly efficacious against intravaginal (IVag) SIVmac239 challenge, providing control and progressive clearance of SIV infection in 59% of vaccinated RMs. Moreover, among 12 ΔRh110 RhCMV/SIV-vaccinated RMs that controlled and progressively cleared an initial SIV challenge, 9 were able to stringently control a second SIV challenge ~3 years after last vaccination, demonstrating the durability of this vaccine. Thus, ΔRh110 RhCMV/SIV vectors have a safety and efficacy profile that warrants adaptation and clinical evaluation of corresponding HCMV vectors as a prophylactic HIV/AIDS vaccine.


Assuntos
Vacinas contra Citomegalovirus/imunologia , Citomegalovirus/imunologia , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Vacinas Atenuadas/imunologia , Animais , Vetores Genéticos/metabolismo , Macaca mulatta , Necrose , Linfócitos T/imunologia , Fatores de Tempo , Resultado do Tratamento , Vacinação
2.
Am J Obstet Gynecol ; 206(6): 456-62, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22244469

RESUMO

Ionizing radiation during pregnancy can negatively impact a fetus. In light of the Fukushima nuclear plant disaster in Japan, we discuss existing knowledge on the health effects of radiation and preventive measures for pregnant women. Overall, the risk of exposure to radiation is limited but severe defects can result from fetal radiation exposure >100 mGy equivalent to 10 rad (>1000 chest x-rays). While such high-level exposure rarely occurs during single medical diagnostic procedures, caution should be exercised for pregnant women. As a protective public health measure in light of a disaster, evacuation, shielding, and elimination of ingested radioactive isotopes should all be considered. Detailed radiation reports with health effects and precautionary measures should be available for a population exposed to more than background radiation.


Assuntos
Desastres , Lesões Pré-Natais/prevenção & controle , Lesões por Radiação/prevenção & controle , Liberação Nociva de Radioativos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Japão , Lactação/efeitos da radiação , Gravidez , Lesões Pré-Natais/diagnóstico , Doses de Radiação , Lesões por Radiação/diagnóstico
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