Identification and validation of immunogenic potential of India specific HPV-16 variant constructs: In-silico &in-vivo insight to vaccine development.
Cervical cancer is one of the most common gynecological cancers in the world but in India, it is the top most cancer among women. Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the most important risk factor. The sequence variation(s) in the most common HR-HPV i.e. HPV type 16 leads to altered biological functions with possible clinical significance in the different geographical locations. Sixteen major variants (V1-V16) in full length L1 gene of HPV-16 were identified following analysis of 250 prospectively collected cervical cancer tissue biopsies and their effect on immunogenicity was studied. The effect of these major variations on the epitopes were predicted by in silico methods and the immunogenicity of variants and respective reference DNA vaccine constructs were evaluated by administration of prepared DNA vaccine constructs in female BALB/c mice to evaluate antibody titer. In the present study, L500F (V16) variation showed a significant ~2.7 fold (p < 0.002) increase in antibody titer, whereas T379P (V8) showed ~0.4 fold (p < 0.328) decrease after final injection. These results showed a promising roadmap for the development of DNA based vaccine and for the generation of effective response, though there is a need to study more prevalent variants of HPV in the Indian population.
Division of Molecular Genetics &Biochemistry; Noida, Uttar Pradesh, India.|Dr. B.R. Ambedkar center for Biomedical Research, University of Delhi (North Campus), New Delhi, India.
Anoop
A
Kumar
Division of Molecular Genetics &Biochemistry; Noida, Uttar Pradesh, India.
Showket
S
Hussain
Division of Molecular Genetics &Biochemistry; Noida, Uttar Pradesh, India.
Gagan
G
Sharma
Division of Cytopathology; Institute of Cytology &Preventive Oncology (ICMR), Noida, Uttar Pradesh, India.
Ravi
R
Mehrotra
Division of Genome Modification and Carcinogenesis, German Cancer Center, DKFZ Heidelberg, Germany.
Lutz
L
Gissmann
Dr. B.R. Ambedkar center for Biomedical Research, University of Delhi (North Campus), New Delhi, India.
Bhudev C
BC
Das
Division of Molecular Genetics &Biochemistry; Noida, Uttar Pradesh, India.
Mausumi
M
Bharadwaj
D000818:Animals; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology*; D003198:Computer Simulation; D005260:Female; D014644:Genetic Variation / Q000235:genetics* / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007194:India; D051379:Mice; D008807:Mice, Inbred BALB C; D030361:Papillomavirus Infections / Q000276:immunology; D015995:Prevalence; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D019444:Vaccines, DNA