Carlos Duque, a molecular biologist from Colombia, proposes developing a next-generation vaccine against all mucosal human papillomavirus (HPV) genotypes. The current HPV vaccines only protect against a small number of genotypes and cannot adapt to new emerging genotypes. Duque believes that by applying evolutionary and structural analysis of HPV genotypes using bioinformatics techniques, it is possible to intelligently design a vaccine that protects against all mucosal HPV types. This new broadly protective vaccine could have a major impact on global public health by eradicating HPV infections and decreasing cancer risks. Duque is seeking a financial partner to help fund a one-year project utilizing bioinformatics to identify immunogenic regions of HPV proteins and model vaccine designs

1. NEW VACCINE DESIGN
CARLOS DUQUE
MOLECULAR BIOLOGIST
Armenia, Colombia
630001
+57 036 7376275
cduque29cx@gmail.com
carlosduque@ula.ve
A N E V O L U T I O N A R Y A N D S T R U C T U R A L V I S I O N I N T H E
D E S I G N O F A V A C C I N E A G A I N S T T H E M U C O S A L A N D
O N C O G E N I C H U M A N P A P I L L O M A V I R U S E S .

2. SMART DESIGN
EVOLUTION
TECHNOLOGY

3. Financial Parther
I am excited to develop a next-generation vaccine against the human papillomavirus.
For more than 5 years I worked at the Universidad de los Andes researching the human
papiloma virus. I addressed topics such as the interaction of caspase 8 with the E2 protein,
production of VLP with the L1 protein of HPV 16, immunization of animals, immunoassays and
bioinformatics (sequence analysis and structural bioinformatics). During the analysis of my
results in my postgraduate thesis I managed to identify a methodology that manages to
corroborate immunoassays with a model in bioinformatics, then I thought about the
usefulness of these analyzes which were directed towards the potential development of a
new vaccine cosiderando evolution and structure of the virus . Maybe it looks like science
fiction but we are very close to the evolutionary impact with the biinformatics techniques and
programs that are being handled today. In these moments I am writing my articles from the
results of the investigation of these years.
When I was an undergraduate I was an assistant professor. I was in charge of preparing the
practices, correcting reports and quizes of a subject called Regulation (biochemistry II)
regulation of gene expression. After graduating the University hired me as a laboratory
supervisor, where I developed as a researcher and learned to manage the programs and
equipment in the laboratory, parallel to this I did my graduate in molecular biology where
product of my degree work I managed to get this analysis for the development of a new
vaccine (eureka ... !!!). It only takes a partner to carry out my dreams where all my will, my
desire and my love are placed.
To be honest,
Carlos Duque
Colombia
+57 036 7376275
C O V E R L E T T E R

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5. CONTENTS
ABSTRACT
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ANTECEDENT
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OBJETIVES
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pg. 5
REISE|PAGE2
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PROBLEM AND SOLUTION
TEAM AND WORKING DEADLINE
pg. 6
INVESTMENT FUNDS REQUIRED
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BUSINESS PROPOSAL
pg. 8
RISKS AND PROBLEMS
pg. 9
REFERENCES

6. The human papillomavirus is a key factor in the development of genital lesions that can cause
cancer. Currently there are 3 prophylactic vaccines based on recombinant natural models
(Virus Like Paritule) that are usually protective only for a small fraction of the genotypes
present in nature that can infect the ano-genital and buccal regions. This vaccine was
designed with a technology of more than 30 years ago and is not adapted to the
appearance of new genotypes as well as to the evolutionary and epidemiological kinetics.
Nowadays, with the appearance of new DNA sequencing techniques (NGS), the genome of
225 genotypes of the virus has been sequenced in which a quarter of them are mucosal of
clinical importance. The availability of these sequences of the virus opens the field to new
evolutionary and epidemiological studies based on new technologies in the field of
bioinformatics and protein and antigen engineering. The use of these tools in order to
achieve an intelligent design of a last generation vaccine capable of neutralizing all
genotypes of mucosal HPV is possible. This new design will have a high impact on the
pharmaceutical industry in the commercialization of vaccines worldwide with high
epidemiological impact.
MSC. CARLOS DUQUE
MOLECULAR BIOLOGIST
A B S T R A C T
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7. Currently there are three prophylactic vaccines with a VLP license of HPV L1 - Cervarix®, a
bivalent vaccine against HPV 16 - 18 of GlaxoSmithKline Biologicals (GSK) and Gardasil®, a
quadrivalent vaccine HPV 16 - 18 - 6 -11 of MSD Merck. (most recent 9 valent). Both vaccines
have been shown in randomized control trials to be effective against HPV 16 -18 causing
high-grade cervical intraepithelial disease (CIN2 / 3) in women aged 15-26 years who have
not been infected with these types of HPV in the entrance and during the immunization
schedule of 3 vaccines (0, 1) or 2 and 6 months) (Kjaer et al., 2009; Dillner et al., 2010).
Additional test endpoints were evaluated for the tetravalent and high (> 96%) vaccine
efficacy was demonstrated for HPV 6- 11 - 16 - 18 (Paavonene et al., 2009). In men aged 16-
23 years, the quadrivalent vaccine has been shown to achieve> 90% efficacy against HPV 6 -
11 - 16 -18 in genital lesions in heterosexual men and> 73% efficacy against anal
intraepithelial neoplasia in homosexual men (Palefsky, 2012 ).
New ecological pressures linked to vaccination . The introduction of vaccines targeting a
subset of the circulating PV diversity implies a dramatic change in the differential ecological
pressures for virus circulation. Therefore, evolutionary and ecological considerations on
vaccines and PV dynamics have both fundamental and clinical implications. Such
considerations address the individual levels of protective immunity caused by vaccination,
the possible generation of collective immunity, that is, the protection against viral infection
in unvaccinated individuals caused through the barrier effect of vaccinated individuals and
the possibility that the pathogen can evade immune restrictions through sequence evolution.
Vaccination with intramuscular viral antigens and the presence of adjuvant molecules that
act as local immune modulators are possibly responsible for the very high level of
seroconversion and high antibody titers compared to those obtained during natural infection
(Doorbar et al. , 2012).
A N T E C E D E N T
2

8. The new ecological and evolutionary pressures linked to vaccination against HPV can cause
the persistent appearance with epidemiological importance of new potentially oncological
genotypes. Current circulating vaccines only offer protection against common types of HPV.
The development of this new vaccine is aimed at offering protection against all mucosal HPV,
thus decreasing the probability of the appearance of new genotypes in the population and
eradicating HPV-associated infections, directly affecting the structural evolution of epitopes
of the virus capsid. through intelligent design.
P R O B L E M A N D S O L U T I O N
3

9. GENERAL
Design the DNA sequence of the L1 protein based on structural and evolutionary studies of
mucosal HPV. Highly immunogenic vaccine model.
O B J E T I V E S
4
SPECIFIC
Identify the immunogenic regions of the HPV L1 protein of all mucosal HPV by
bioinformatics
To carry out an evolutionary and structural study of the immunogenic regions of the capsid
Model three-dimensional structures associated with the L1 protein of HPV.
Make studies of structural superpositions
Organize the data
Locate hot sites and do genetic engineering by bioinformatics.

10. TEAM
Carlos Duque. Project coordination and execution.
Administration of financing funds, research and development of the project, analysis of
results, evaluation and design, presentation of oral and written advances.
Two research assistants (to be defined). Molecular study of the L1 prtein, obtaining
information from the database, analysis of sequences and structure by bioinformatics,
overlays, delivery of results to the coordination
Programmer (to be defined). Organization of data that requires programming in python.
Financing partner. Observer of advances, mentor, suggestions, coordination of online
meetings, receiver.
WORKING DEADLINE
T E A M A N D W O R K I N G D E A D L I N E
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11. I N V E S T M E N T F U N D S R E Q U I R E D
6

12. FINANCIAL PARTNER
The development of a new vaccine implies a business of millions of dollars for the
pharmaceutical and biotechnology industry. The new design of a vaccine against HPV is
patentable. Said patent can then be sold or continue in the development phase of the
vaccine with tests in the laboratory.
The financing partner will have 50% of the rights over said patent that can then be sold and
go on to the second phase of vaccine development.
The partner and the developer of the idea will be willing to sign a private financing contract
where both parties assume resposibilities in the project as well as in future patents that
involve a high income of money.
B U S I N E S S P R O P O S A L
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13. Undoubtedly the pharmaceutical and biotechnology industry are working on the development of a
new vaccine, however they may or may not share the same vision that this project uses based on the
evolutionary incidence of the structure of the human papillomavirus. Therefore it is a competitive area
and one works over time.
The design of this new vaccine is estimated in one year or less.
The business idea to assume after the design is to obtain a patent and then go on to the
production and testing phase of the vaccine in a laboratory, which implies new sources of
financing to complete its development and obtain the license in the FDA. It requires
negotiation.
R I S K S A N D P R O B L E M S
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14. Doorbar J, Quint W, Banks L, Bravod I, Stolere M, Brokerf T, Stanleyg M. (2012) The Biology
and Life-Cycle of Human Papillomaviruses. Vaccine 30S F55– F70.
Palefsky J.M., Goldstone S., Moreira E.D., Jr., Vardas E. Immunogenicity of the quadrivalent
human papillomavirus (type 6/11/16/18) vaccine in males 16 to 26 years old. Clin. Vaccin.
Immunol.: Cvi. 2012;19:261–267.
Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, et al (2009) Efficacy of
human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and
precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind,
randomised study in young women. Lancet, 374:301-314
Kjaer SK, Sigurdsson K et al. (2009) The impact of quadrivalent human papillomavirus (HPV;
types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic
nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis;199:926–
35.
Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez- Avila M, et al: (2010)
Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low
grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts:
randomised controlled trial. BMJ, 341:c3493.
R E F E R E N C E S
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15. “THERE IS A DRIVING FORCE MORE POWERFUL THAN STEAM,
ELECTRICITY AND ATOMIC ENERGY: THE WILL.”
ALBERT EINSTEIN