The use of peptides for studying molecular events in HIV- and HSV-infections
Author: Levi, Michael
Date: 1997-12-17
Location: Föreläsningssalen vid Mikrobiologiskt och Tumörbiologiskt Centrum, Doktorsringen 13, Karolinska institutet
Time: 9.00
Abstract
Synthetic peptides were used as tools in order to study various
characteristicsof human immunodeficiency virus (HIV) and herpes simplex
virus (HSV). Peptides weredesigned as multiple antigenic peptides (MAPs)
and used as HIV vaccines in experimentalanimals. The included HIV
epitopes were more immunogenic when immunized as MAPs thanas a protein.
This was probably due to the fork-like MAP structure which gave
aneffective multimeric epitope delivery to the immune cells. The
anti-peptide anbbodiesalso bound to the protein and showed biological
activity.
An accurate antibody population profile is crucial in order to evaluate
differentvaccine candidates. Specific antibody populations in HIV
envelope protein gpl60-vaccinatedanimals, HIV infected patients or
untreated infected patients from Sweden and Argentina,were analyzed. A
broad vaccine-induced antibody production in immunized animals anda
slight expansion of the existing immunity in vaccinated HIV-infected
humans. Anew immunodominant region of the HIV envelope was identified,
against which the majorityof HIV seropositive Swedish and Argentinian
patients showed reactivity. By usingpeptides the HIV-specific antibody
pool could be mapped in detail which was not possibleby using the entire
gpl60 protein. A comparison of different adjuvants revealed thatthe
muramyl dipeptide (MDP) and proteosome adjuvants were potent enhancers of
immunityagainst the HIV envelope protein gpl60.
A mini antibody was designed, corresponding to a complementarity
determining region(CDR) in the antigen-binding domain of an HIV-specific
antibody with neutralizingcapacity. The CDR peptide competed with the
whole antibody for its epitope, locatedin the third variable loop (V3) of
the HIV envelope protein gpl20. The mini antibodyalso showed broad
neutralization of both laboratory-adapted virus and primary isolates.This
CDR peptide appeared to cross cellular membranes and may be capable of
inactivatingviral envelopes intracellularly. It might be used to treat
HIV-infected individualsand should induce less side effects and spread
more effeciently than whole antibodies.
The interaction between the HIV envelope protein gpl20 and its cellular
co-receptorCCR5 was analyzed. CCR5 mediates a which is a post-binding
interaction necessaryfor cellular fusion. Strong binding of gpl20 was
seen against peptides representingthe N-terminal and first extracellular
loop regions in CCR5. In addition, the N-terminalCCR5 domain peptide
bound strongly to the V3 loop of gpl20, which is the major
neutralizationdeterminant of HIV. Both the N-terminal CCR5 peptide and
peptide-induced rabbit immunesera showed specific inhibition of viral
replication. This indicates a possibilityto treat HIV-infected patients
with CCR5 peptides that block the post binding fusionstep.
Discrimination between herpes simplex virus type 1 (HSV-I) and type 2
(HSV-2)infection is important in prevention of virus transmission. Sites
of HSV glycoproteinswere analyzed for their potency for serodiagnosis of
latent HSV infection. Peptidesfrom the glycoproteins G (gG) and D (gD)
proteins showed promise as HSV-2 specificand HSV type-common antigens
respectively. Interestingly, the most homologous regionof HSV-1 / HSV-2
gG was highly discriminating and with sensitivities and
specificitiessimilar to native antigens. These peptides may be developed
into HSV diagnostic tests.
ISBN 91-628-2784-7
Issue date: 1997-11-26
Publication year: 1997
ISBN: 91-628-2784-7
Statistics
Total Visits
Views | |
---|---|
The ...(legacy) | 147 |
The ... | 24 |
Total Visits Per Month
July 2020 | August 2020 | September 2020 | October 2020 | November 2020 | December 2020 | January 2021 | |
---|---|---|---|---|---|---|---|
The ... | 2 | 1 | 1 | 2 | 1 | 3 | 1 |
Top country views
Views | |
---|---|
United States | 36 |
Germany | 35 |
China | 21 |
Sweden | 12 |
South Korea | 6 |
Hong Kong | 4 |
Russia | 4 |
Denmark | 3 |
Finland | 3 |
Greece | 2 |
Top cities views
Views | |
---|---|
Kiez | 15 |
Seoul | 6 |
Sunnyvale | 6 |
Tianjin | 4 |
Woodbridge | 4 |
Ballerup | 3 |
Beijing | 3 |
Easton | 3 |
Athens | 2 |
Dublin | 2 |