Download Update and New Perspectives on HSV Infections, Paulo R. Cunha

21st World Congress of Dermatology
Oct/2007
“Update
and new
perspectives on HSV
infections”
Paulo R. Cunha, MD, PhD.
Professor of Dermatology
Jundiaí Medical School
São Paulo, Brazil
Introduction
Over 70% of the population has been infected
by either HSV-1 or HSV-2
Produce: primary, latent and recurrent
infections.
Clinical manifestation: “benign and malign”
Extragenital Herpes:
80-90%: HSV-1
Genital Herpes: (normally sexual transmission)
80-90%: HSV-2
DNA Virus
Serological techniques:
HSV-1: glycoprotein gC1
HSV-2: glycoprotein gC2
Keratinocyte
Cytoplasm
Herpes
virus
Capsid
DNA HSV
Capsomers
Cell membrane
Virus new
particle
Acyclovir
Cytoplasmic Membrane
Timidina
Kinase (TK)
Acyclovir
Monophosphate
Acyclovir
Triphosphate
Genital Herpes: CDC Treatment
Recommendations
First clinical
genital herpes
episode
(mg for 7–10 days)
Valacyclovir
Acyclovir
Famcyclovir
1000 bid
400 tid
200 5/day
250 tid*
Recurrent genital herpes
episodic
suppressive
(mg  days)
(mg, daily)
500 bid (3†-5 d)
500 qd‡
1000 qd (5 d)
1000 qd
400 tid (5 d)
800 bid (5 d)
200 5/day (5 d)
125 bid (5 d)
400 bid
250 bid
up to 1 year
*Not FDA approved
†New FDA-approved dosing
‡May be less effective in patients who have very frequent recurrences (10 episodes/year)
Centers for Disease Control and Prevention. MMWR. 2002;51(RR-6)12-17.
Issues to be considered in
Suppressive Therapy
Not necessary to wait 6 outbreaks
in 12 months
Define impact of genital herpes
Gravity and duration of the
outbreak
New Therapeutic Options
1) Analog of nucleoside
Cidofovir (gel 0.3 or 1%) Single-dose
confers a significant antiviral effect on
lesions of recurrent genital herpes.
Antimicrob Agents Chemother 1998 Nov;42(11):2996-9
New Therapeutic Options
2) Immunomodulator
Resiquimod (gel 0.05%) Significant
reduction in number of recurrences
J Infect Dis 2001 Jul 15;184(2):196-200
New Therapeutic Options
3) Fusion Inhibitor
Docosanol (Abreva®) (cream 10%)
interferes with the process of viral
fusion with the host cell.
Effective treatment for recurrent
HSL.
J Am Acad Dermatol 2001 Aug; 45 (2): 222-30)
New Therapeutic Options
4) Direct action in DNA polimerase of HSV
Foscarnet is the choice in pts with HSV
resistant to acyclovir. It is effective in
destroying the virus timidina kinase
lacking (nephrotoxicity).
Rio Dermatológico 2001 July/August/September
Foscarnet (cream 2%) is an effective and
safe medication in the treatment of
HSL.
Hautarzt. 2006 Jan;57(1):40-6
New Therapeutic Options
5) Helicase inhbitors
(Phase III)
Could increase the
intervals between
the crises and it
is more effective
then acyclovir
Nature Med. 8,392-398, 2002). (Phase III)
Treatment of Recurrent Herpes Simplex
with L-Lysine
Decreases recurrence and severity
Long-term: L-Lysine 1 g/day
Avoid: Arginine, “Herpetogenic” foods like
chocolate, peas, cola drinks, grain cereals,
peanuts, gelatin, cashews, beer.
Encourage: Lysine, Foods like dairy products,
milk, potatoes, brewer’s yeast.
New Antiherpes Vaccines
by Genetic Engineering
An ideal vaccine should induce Cellular and Humoral
Immune Response adequate to prevent infection.
Vaccines by genetic engineering
PCMV T7His6EK BGH f1 SV40 N SV40 ColE1
pA ori ori
pA
Amp
Vaccines with DNA of plasmid that contains the codes of
viral glycoproteins (pcDNA3.1/His A,B,C 5.5 kb )
Plasmid insertion
Chromosome
transformed
bacteria
Plasmid
transference
Cellular and Humoral Immune
Response
Herpes Virus Vaccine:
News and Perspectives
The most hopeful result was obtained with HSV-2
gD2 and alum/MPL vaccine (Glaxo SmithKline) in clinical
studies.
-74% effective in preventing genital disease
-Only in women who had never been exposed to HSV
previously.
-Not effective in men
Herpes Virus Vaccine:
News and Perspectives
DISC (Disabled Infectious Single Cycle) virus
HSV vaccine contains a virus with deletion of
an essential gene (gH gene), so the replication
has been limited to a single cycle only. Guinea
pigs were protected from a primary infection.
Significant protection from recurrent disease
was also observed.
Herpes Virus Vaccine Studies
Prophylactic Vaccines for HSV-2
Genetically engineered HSV to produce a vaccine that is protective
without causing human disease is in development. Using a vaccine
with live attenuated HSV from which neurovirulence gene (gamma
1 34.5) has been removed, has debilitated HSV in its ability to
establish latency and be reactivated.
Animals vaccinated are able to elicit protective immune responses
Mikrobiyol Bul. 2006 Oct;40(4):413-33
Conclusions
HSV Vaccine is still a challenge.
Seronegative individuals at high risk for infection represent
ideal candidates for vaccine trials.
Individuals with frequent recurrences are not significantly
responsive to vaccines so far.
Promising approaches to engineered HSV vaccines should be
possible within the next several years.
We are in the right road but we have to keep walking.
Sexual education, campaigns of information and the use of
preservative continues to be essential.
Thank you!
[email protected]