potential development of inactivated hiv-1 transmitted...

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

Thank you!

Adan Rios, MDadan.rios@uth.tmc.edu

Cellphone 713-829-8153

Office 713-500-7766