State
of Current AIDS Vaccine Research
:
Reproduced with
permission from www.iavi.com (International association of vaccines and
Immunology)
LEFT : Electron microscopic image of HIV viruses. Note the dark
core and comparitively lighter periphery. Click on the image for a larger
picture.
You
might find it useful to review the structure of the HIV virus (click
here) before continuing.
Given the scale of the AIDS pandemic and the long lead time required for
development and distribution of an AIDS vaccine, the number of products now in
clinical testing is woefully inadequate. After more than 15 years of research on
HIV, only one vaccine concept is being tested for efficacy in and only one other
type of vaccine has entered Phase II trials. Equally serious is the shortage of
vaccine candidates currently undergoing Phase I trials, the necessary precursors
to the later tests. Although there
are different designs that might lead to a useful AIDS vaccine, most of them
have in common that they use specific parts of HIV (genes or proteins) to
activate the body's immune defenses. Once the immune system has learned to
recognize these viral components, the hope is that it can mount a vigorous
defense when it encounters the real virus.
The following list summarizes the different concepts currently being
tested as candidate AIDS vaccines.
1)
Recombinant subunit vaccines:
introduce
a harmless subunit (portion) of an HIV protein into the body. This is the basis
of AIDSVAX, the first vaccine being tested for effectiveness in humans and which
is made from a portion of HIV's outer surface (envelope) protein, called gp120.
The hepatitis B vaccine successfully uses this approach to confer protective
immunity.
Candidate
recombinant subunit vaccines for AIDS in clinical trials:
gp 120: Phase III p24: Phase I
2)DNA
vaccines:
also
known as "naked DNA" or "nucleic acid" vaccines, use the
actual genes of HIV as a vaccine. Once introduced into skin or muscle, the
genetic material is taken up by cells in the body, which then produce HIV
proteins that stimulate the immune system. Several experimental vaccines s using
this new technology against other diseases have successfully protected animals,
including experimental SIV vaccines in monkeys.
Current
status of DNA vaccines for AIDS in clinical trials: Phase I
3)Live
recombinant viral vector vaccines:
are created by
genetically engineering relatively harmless, replicating viruses to produce HIV
proteins, which then stimulate HIV-specific immune responses. Many HIV vaccine
candidates now in development are made with some type of viral vector. These
include the alphavirus vectors (Venezuelan Equine Encephalitis; Sindbis or
Semliki Forest viruses); adenovirus; adeno-associated virus (AAV); and pox
viruses (e.g. canarypox; fowlpox, modified vaccinia Ankara [MVA] and vaccinia).
Despite this significant preclinical activity, only two viral vector strategies
have thus far reached clinical trials. One of them, the canarypox-based
vaccines, may be the next concept to reach large-scale efficacy trials.
Candidate
live recombinant viral vector vaccines for AIDS in clinical trials:
Canarypox: Phase II Vaccinia: Phase I
4)Live
recombinant bacterial vector vaccines
are similar in concept to viral vector vaccines, except that the HIV
genetic material is molecularly engineered into bacteria rather than viruses.
Potential advantages are that this type of vaccine can usually be produced
cheaply, and that it can be given orally rather than injected. Several bacterial
systems are currently being evaluated for their potential as AIDS vaccines.
These include Salmonella, Shigella, Listeria, and BCG.
Candidate
live recombinant bacterial vector vaccines for AIDS in clinical trials:
Salmonella: Phase I
5)Live-attenuated
vaccines
are used globally against many viral diseases, such as polio (Sabin
vaccine) and measles. They consist of weakened (attenuated) but living virus
that is too disabled to cause disease but can still infect cells and replicate
within the body. By learning to respond to weakened virus, the immune system can
then protect against the full-strength, disease-causing strain. In monkeys,
live-attenuated SIV vaccines have proven to induce protective immunity against
SIV far more consistently than any other type of vaccine. Safety is a serious
concern, however, because of well-documented instances of AIDS occurring in a
small percentage of monkeys inoculated with certain strains of live-attenuated
SIV vaccines.
Candidate live-attenuated AIDS vaccines in clinical trials:
NONE
6)Whole-inactivated
vaccines
are used worldwide against many viral diseases, including polio (Salk
vaccine), hepatitis A and influenza. The advantage of this approach is that it
presents the entire viral particle to the immune system, which therefore
"sees" the full spectrum of viral proteins. Yet the virus cannot
infect and replicate, making this a safer approach than live-attenuated
strategies. But for a variety of reasons, including some technical difficulties,
it has not been widely pursued for HIV.
Candidate whole inactivated AIDS vaccines in clinical
trials: NONE
7)Virus-like
particle vaccines
are made
by using several different HIV proteins engineered to mimic an HIV particle.
Studies have shown that these incomplete viral particles can stimulate both
antibody and cellular immune responses, and are safe and immunogenic.
Candidate virus-like particle vaccines for AIDS currently
in clinical trials: NONE
8)Synthetic
peptide vaccines
consist of very small portions of HIV proteins chosen specifically to focus the
body's anti-HIV immune responses on what are thought to be the most potent
immunity-inducing regions of the proteins. Extensive basic research has shown
that the immune system will mount a response to certain very short protein
segments (called peptides) when these peptides are displayed appropriately to
the immune system.
Candidate synthetic peptide vaccines for AIDS in clinical
trials p17:
Phase I Lipopeptides: Phase I V3-based: Phase I
9)”Jennerian"
vaccines:
In the 18th century, Edward Jenner discovered that immunization with cowpox
protected people against variola virus, the cause of smallpox in humans. This
concept of "Jennerian" vaccines, based on using similar but
non-identical viruses to those that cause disease, is being explored for HIV.
Possibilities include the simian equivalent of HIV (called SIV); a weaker strain
of HIV called HIV-2; and lentiviruses from other species, such as the caprine
arthritis encephalitis virus (CAEV).
10)Complex
vaccines
attempt to direct immune responses to the human host cell receptors that serve
as HIV's port of entry into cells, rather than to HIV itself. The idea is that
by blocking HIV receptors (such as the CD4 or CCR5 molecules), virus will be
unable to attach to the cell surface or to infect cells.
Candidate
Jennerian or complex vaccines in clinical trials: NONE
11)Combination
vaccines:
use two or
more of the above approaches, based on the premise that this could induce a
broader spectrum of immune responses than any single approach. One combination
now in phase II trials uses a canarypox viral vector together with a gp120
subunit from HIV's outer surface. Another combination strategy uses a DNA
vaccine to "prime" the immune system and an MVA vaccine to
"boost."
Current
status of combination vaccines for AIDS in clinical trials: Canarypox +
gp120: Phase II
