potential development of inactivated hiv-1 transmitted...
TRANSCRIPT
Potential Development of
Inactivated HIV-1 Transmitted/
Founder Virus (T/F) Vaccine
Dr. Adan RiosDivision of OncologyDepartment of Internal Medicine
Two extravagances:To exclude Reason,
To admit only Reason
Blaise Pascal
2
SGA and the Eclipse Phase
PNAS. 2008. Vol 105 No21: 7552-7557
Transmitted Founder (T/F) Viruses
• 80% of heterosexual of all HIV-1
infections are established by a single T/F
virus
• 24% by at least two to five viruses. This
is consistent with a relative inefficiency
of virus transmission by most sexual
routes
PNAS. 2008. Vol 105 No21: 7552-7557
Population Bottleneck Effect on
Frequency distribution in a Viral
Quasispecies Population
High Affinity of Germline Precursor Antibody for T/F Envelope
Nature. 2013. Vol496:441-442
High Affinity of Germline Precursor
Antibody for T/F Envelope
Nature. 2013. Vol496:441-442
Reverse Transcriptase Inactivation
The First Molecule
Vaccine 27 (2009) 6137-6142
N3
Photo-label Compound : PA-DAPYa*
*diarylpyrimidine analogue
J. Virol. Methods Vol 189 (2013):125-128
Virus Research 2011 155 189-194
Inactivation of HIV- photolabeled NNRTI
Suspension of Virus Treated with UV Light
250
200
150
100
50
Virus alone
3
J. Virol. Methods Vol 189 (2013):125-128
No UV exposureUV Time 10UV Time 30UV Time 40UV Time 60
Pre-treatment with C-DAPY
250
200
150
100
50
C-DAPYa Compound Concentration (nM)
3
P24
(pg
/ml)
5 50 100 200 500
No UV exposureUV Time 10UV Time 30UV Time 40UV Time 60
J. Virol. Methods Vol 189 (2013):125-128
Pre-treatment with PA-DAPY
250
200
150
100
50
PA-DAPYa Compound Concentration (nM)
3
P24
(pg
/ml)
5 50 100 200 500
No UV exposureUV Time 10UV Time 30UV Time 40UV Time 60
J. Virol. Methods Vol 189 (2013):125-128
SF162.LS HIV-1
PA-DAPYa*
Non-microbicidal UV light (365nm)
*diarylpyrimidine analogue
At the NIH
T/F Viruses Conserved Molecular
Signatures
J. Virol. January 14 2015 Posted on line
Comparison of vaccinated vs. control T/F Envs,
intrarectal vs. intravaginal T/F Envs.
J. Virol. doi:10.1128/JVI.02711-15Online 16 December 2015
Neutralization of T/F virus is key to the prevention of HIV transmission
If the founder virus is
neutralized by Abs present in
the host at the time of HIV
exposure the infection by HIV
should be effectively
prevented.
Conclusions
“The evidence of selection on gp120 molecules of SIV/SHIV/HIV T/F viruses suggests they are potential targets for developing a preventive HIV vaccine.”. Gonzalez MW, De Vico AL, Lewis GK, Spencer JL.
in J. of Virology. 2015;Vol 89:3619-3629.
“The methodology of the present invention is applicable to any retrovirus which may be associated with any animal or human diseases as a method for development of effective immunogens and preventive vaccines”
Rios A. in Method for Development of a Preventive HIV vaccine. Serial number: 10/667,534.
“Nothing in biology makes sense
except in the light of evolution”
Theodosius Dobzhansky (1973)
21
Collaborators
� McGill AIDS Centre
Montreal
� Mark A. Weinberg
� Susan Colby-Germinario
� Baylor College of Medicine
Houston
� Qizhi C. Yao
� Edward B. Siwak
� Ethan C. Poteet
� Chistian Marin-Muller
� George Washington
University Washington DC
� Alan Goldstein
� Texas A&M University
College Station
� Theresa Fossum
� University of Texas Medical
School Houston
� Jorge Quesada
� PhotoImmune
Biotechnology
� Dallas W. Anderson
� Hitar Synthesis Poland
� Jaroslaw Kiegiel
� Special Thanks
� Rev. George Foreman
