کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1317706 1499470 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Detection of human papillomavirus (HPV) L1 gene DNA possibly bound to particulate aluminum adjuvant in the HPV vaccine Gardasil®
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Detection of human papillomavirus (HPV) L1 gene DNA possibly bound to particulate aluminum adjuvant in the HPV vaccine Gardasil®
چکیده انگلیسی

Medical practitioners in nine countries submitted samples of Gardasil® (Merck & Co.) to be tested for the presence of human papillomavirus (HPV) DNA because they suspected that residual recombinant HPV DNA left in the vaccine might have been a contributing factor leading to some of the unexplained post-vaccination side effects. A total of 16 packages of Gardasil® were received from Australia, Bulgaria, France, India, New Zealand, Poland, Russia, Spain and the United States. A nested polymerase chain reaction (PCR) method using the MY09/MY11 degenerate primers for initial amplification and the GP5/GP6-based nested PCR primers for the second amplification were used to prepare the template for direct automated cycle DNA sequencing of a hypervariable segment of the HPV L1 gene which is used for manufacturing of the HPV L1 capsid protein by a DNA recombinant technology in vaccine production. Detection of HPV DNA and HPV genotyping of all positive samples were finally validated by BLAST (Basic Local Alignment Search Tool) analysis of a 45–60 bases sequence of the computer-generated electropherogram. The results showed that all 16 Gardasil® samples, each with a different lot number, contained fragments of HPV-11 DNA, or HPV-18 DNA, or a DNA fragment mixture from both genotypes. The detected HPV DNA was found to be firmly bound to the insoluble, proteinase-resistant fraction, presumably of amorphous aluminum hydroxyphosphate sulfate (AAHS) nanoparticles used as adjuvant. The clinical significance of these residual HPV DNA fragments bound to a particulate mineral-based adjuvant is uncertain after intramuscular injection, and requires further investigation for vaccination safety.

Human papillomavirus (HPV) L1 gene DNA fragments were detected by degenerate primer PCR in all 16 Gardasil® vaccine samples tested. The HPV DNA was possibly attached to the insoluble amorphous aluminum hydroxyphosphate sulfate (AAHS) adjuvant firmly via a chemical bond. DNA sequencing confirmed that the DNA fragments detected were those of an HPV-11 L1 gene or an HPV-18 L1 gene, or a mixture of both.Figure optionsDownload as PowerPoint slideHighlights
► All 16 Gardasil® vaccine samples tested contain residual HPV L1 gene DNA fragments.
► The HPV DNA fragments are bound to particles possibly of aluminum adjuvant.
► The bond between the HPV DNA and the particles may be chemical in nature.
► All HPV DNA fragments detected by nested PCR were confirmed by DNA sequencing.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 117, December 2012, Pages 85–92
نویسندگان
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