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New Concepts for Vaccines1
Trudy V. Murphy,*
Gary Dubin,† Robert B. Belshe,‡ Thomas P. Monath,§ Irene B. Glowinski,¶
Susan A. Daniels,¶ and Joel C. Gaydos#
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †GlaxoSmithKline,
King of Prussia, Pennsylvania, USA; ‡St. Louis University Health Sciences
Center, St. Louis, Missouri, USA; §Acambis Inc., Cambridge, Massachusetts,
USA; ¶National Institutes of Health, Bethesda, Maryland, USA; and #Department
of Defense Global Emerging Infections Surveillance and Response System,
Silver Spring, Maryland, USA
Suggested
citation for this article
New technologies have created opportunities to develop novel vaccines,
including vaccines for sexually transmitted infections, influenza, and
arthropodborne viruses. A GlaxoSmithKline (GSK) vaccine for genital herpes
combines a recombinant herpes simplex virus (HSV) glycoprotein D (gD)
with AS04, a novel proprietary adjuvant containing aluminum salts, and
3-deacylated monophosphoryl lipid A. Two recently completed efficacy trials
with the gD-AS04 vaccine demonstrated protection against infection with
genital herpes in HSV-1 and -2 seronegative women, but not in seronegative
men. Herpes simplex DNA and live attenuated or replication-impaired virus
vaccines are in early development. Human papillomavirus (HPV) vaccine
uses L1 virus-like particles (VLP) to immunize against HPV-16 and -18,
two oncogenic types of HPV responsible for most cervical cancers. A HPV-16
L1 VLP vaccine (Merck Research Laboratories) and an HPV-16/18 L1 VLP vaccine
(GSK) have recently been shown to prevent infection with the corresponding
HPV types. In a double-blind, placebo-controlled efficacy trial, the GSK
vaccine induced type-specific antibody responses that were higher than
elicited by natural infections and resulted in protection against incident
and persistent HPV-16 and -18 infections. Additional challenges for vaccines
against sexually transmitted infections include assessing the duration
of protection, identifying optimal target populations, and designing implementation
strategies.
Cold-adapted, live attenuated strains of influenza have been developed
in the United States (CAIV-T/USA) and Russia (CAIV-T/Russia) for use as
vaccines. From master donor strains of influenza A or B, reassortant viruses
can be produced annually with contemporary hemagglutinin (HA) and neuraminidase
(NA) from wildtype influenza and six internal genes from the attenuated
strains. Reactogenicity of the reassortants is generally mild; effectiveness
is high. Expanded age indications are expected. Reverse genetics may be
employed in the future to rapidly generate PR-8–based reassortant viruses.
Reverse genetics could be used to eliminate the polybasic cleavage site
of highly pathogenic avian influenza viruses and to rapidly make the PR-8
reassortants. New approaches to trivalent inactivated vaccine include
high-dose HA vaccines, synthesis of recombinant HA antigen, addition of
adjuvants, and intranasal transdermal administration and tissue culture
production of whole viruses. Tissue culture production of antigen could
shorten production time, increase the quantity of antigen, and exactly
match the genetic sequence of HA in circulating viruses. Recombinant HA
is effective as an immunogen and would reduce the reactogenicity associated
with egg-grown trivalent inactivated vaccine. Use of adjuvants has the
potential to stretch the vaccine supply in the event of vaccine shortage.
Platform technology makes use of live, recombinant viruses or bacteria
to express one or more foreign genes that encode the antigen(s) of interest
to deliver naked DNA encoding the vaccine antigen(s). The live vector
may or may not be replication competent. Examples of such vector platforms
include poxviruses, adenoviruses, alphavirus replicons, flaviviruses,
and enteric bacteria (e.g., Salmonella, Lactobacillus).
Preexisting immunity to the vector can limit the effectiveness of this
approach, except with flaviviruses. In flavivirus vectors, e.g., yellow
fever 17 D vaccine-virus platform, the genes encoding the antigens of
the vector are entirely replaced by the genes of interest, e.g., West
Nile virus, St. Louis encephalitis, Japanese encephalitis, or dengue virus.
In clinical trials, several of these "chimeric" viral vaccines
have been well-tolerated and highly immunogenic in clinical trials.
1Presented at the International Conference
on Emerging Infectious Diseases, Atlanta, Georgia, February 29 –
March 3, 2004, by Gary Dubin, GlaxoSmithKline; Robert Belshe, St. Louis
University Health Sciences Center; and Tom Monath, Acambis Inc.
Suggested citation
for this article:
Murphy TV, Dubin G,
Belshe RB, Monath TP, Glowinski IB, Daniels SA, et al. New concepts for
vaccines. Emerg Infect Dis [serial on the Internet]. 2004 Nov [date
cited]. Available from http://www.cdc.gov/ncidod/EID/vol10no11/04-0797_06.htm
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