Abstract
A same-nested PCR was used to re-amplify the amplicon of a hypervariable region of the HPV-16 L1 gene DNA in the postmortem blood and splenic tissue obtained at autopsy of a formerly healthy teenage girl who suffered a sudden unexpected death in sleep 6 months after 3 intramuscular injections of a quadrivalent HPV vaccine, Gardasil?. A full autopsy analysis revealed no cause of death. The HPV-16 gene DNA detected in the postmortem materials was similar to the HPV-16 gene DNA fragments in Gardasil? in that both were in non-B-conformation, requiring nondegenerate GP6 and MY11 primers to re-amplify the PCR amplicon for detection and to generate a template useful for direct DNA sequencing. A sequence excised from the base-calling DNA sequencing electropherogram was analyzed by Basic Local Alignment Search Tool (BLAST) alignment and a 45 - 60 base sequence fully matched with a standard hypervariable region of the HPV-16 L1 gene retrieved from the National Center for Biotechnology Information database validated the correct genotyping for HPV- 16 L1 gene DNA. These naked non-proliferating HPV- 16 L1 gene DNA fragments appeared to be in the macrophages of the postmortem blood and spleen, and were protected from degradation by binding firmly to the particulate aluminum adjuvant used in vaccine formulation. The significance of these HPV DNA fragments of a vaccine origin found in post-mortem materials is not clear and warrants further investigation.
Highlights
Virus-like particles (VLPs) of human papillomavirus (HPV) are irregularly shaped 30 - 50 nm structures composed of self-assembled HPV major capsid L1 protein pentamers manufactured by a DNA recombinant technology [1,2]
The HPV-16 gene DNA detected in the postmortem materials was similar to the HPV-16 gene DNA fragments in Gardasil® in that both were in non-B-conformation, requiring nondegenerate GP6 and MY11 primers to re-amplify the PCR amplicon for detection and to generate a template useful for direct DNA sequencing
A sequence excised from the base-calling DNA sequencing electropherogram was analyzed by Basic Local Alignment Search Tool (BLAST) alignment and a 45 - 60 base sequence fully matched with a standard hypervariable region of the HPV-16 L1 gene retrieved from the National Center for Biotechnology Information database validated the correct genotyping for HPV16 L1 gene DNA
Summary
Virus-like particles (VLPs) of human papillomavirus (HPV) are irregularly shaped 30 - 50 nm structures composed of self-assembled HPV major capsid L1 protein pentamers manufactured by a DNA recombinant technology [1,2]. The recent revelation that Gardasil® does contain recombinant HPV L1 gene DNA fragments [8,9] which appear to be firmly bound to AAHS nanoparticles [9] may offer a plausible explanation for the high immunogenicity of Gardasil® because co-delivery of both a DNA component and a protein component of a vaccine with aluminum phosphate salts may have the advantage of stimulating a potent and multivalent immune response [10]. A number of cases of possibly immune-based inflammatory neurodegenerative disorders involving the central nervous system, known as acute disseminated encephalomyelitis, following Gardasil® injections have been reported in world literature [12,13,14,15,16,17,18].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
