Three general approaches are used for preparation of conventional
vaccines against viral and bacterial infection. Most of the
traditional types of vaccines developed for use in humans are
based on replicating pathogens that have been attenuated (e.g.
vaccinia, polio, measles) or inactivated (e.g. Influenza, rabies,
vibrio cholerae). Another type of vaccine uses detoxified toxins
with formalin to convert it to toxoids (tetanus, diphtheria).
Unfortunately, using whole micro-organisms as a vaccine may
be accompanied by the risk of contaminants and undesirable
responses induced by certain sub-units of the pathogens. Although,
conventional vaccines can induce a strong humoral immunity,
they are less effective, or rather inefficient, against those
micro-organisms that require both antibody- and cell-mediated
responses to achieve good protection.
Another vaccine approach based on sub-units (proteins or peptides)
of micro-organisms was developed in the ‘80's.
This approach has the advantage of generating an immune response
directed only towards the relevant protein or epitope of the
pathogen and may therefore avoid any toxicity or harmful reaction
induced by other immunogenic components of the pathogen. Today,
advanced technology allows the synthesis of well-defined immunogenic
peptides at low cost in a reproducible manner. One very interesting
aspect of the peptide-based vaccine strategy is the possibility
of using multiple antigenic peptides. However, injection of
peptide alone is not sufficient for the induction of a strong
immune response. In order to generate a strong response, the
peptide must be associated with an immunostimulant or an immunogenic
carrier such as an adjuvant. At present, aluminum hydroxide
is the only widely used adjuvant for humans. However, not all
peptides or proteins can be adsorbed well onto aluminum hydroxide.
In addition, cellular response is only slightly stimulated
by alum while the humoral response is efficiently induced.
In the 90's, a novel vaccine consisting of plasmids DNA
encoding for a known antigenic protein was developed and has
been applied to HIV. DNA vaccination has received much attention
as a possible broad-based, inexpensive approach to vaccine
development. There are, however, inconveniences to this approach,
one being the possibility that the plasmid DNA may integrate
into the host genome. Finally, most conventional vaccines require
multiple recall injections at appropriate time intervals in
order to achieve sustained and optimal immune responses. However,
it is time-consuming and very difficult, especially in developing
countries such as Africa where AIDS is pandemic, to maintain
a high re-immunization rate in the case of multiple injections
for a given immunization program.
One way to overcome the above-mentioned problem is to convert
conventional multiple-doses vaccine to a single or two-dose
vaccine, which can be based on multiple subunits of the pathogen
and could contain proteins and/or peptides already present
in the vaccine or synthesized by the cells of DNA vaccinated
subjects. Several HIV-1 vaccine approaches are currently under
investigation and results are expected in the coming years.
Among the approaches under evaluation, the « prime-boost » vaccination
is very attractive because the administration of the same or
similar antigen in two different vectors given successively
might improve the immune repertoire against HIV-1. Exposure
to the antigen in the first vector « primes » the
immune response; re-exposure to the same antigen in the second
vector « boosts » the response. This approach has
also been termed « heterologous boosting », to
distinguish it from the traditional method « homologous
boosting » in which two or more doses of the same vaccine
are given successively.
Developing multi-clade (A, B, C, D, F, G, H, J, K, others)
vaccines containing antigens from two or more HIV-1 subtypes
represent certainly an attractive strategy for future HIV candidate
vaccines. A good HIV vaccine should induce the broadest possible
spectrum of immune responses: cellular responses through testing
a variety of DNA and viral vector-based vaccines and better
defining the most useful HIV antigen. Broadly neutralizing
antibodies by developing novel envelope-based antigens. Like
many other scientists and research groups, Mymetics believes
that successful protection against HIV-1 resides probably in
the development of vaccines that will combine both cellular & humoral
responses. However, to induce such protective responses, Mymetics
strongly believes that it is crucial to prevent the potential
induction of auto-immune response toward the IL-2 for generating
a good and long-lasting immune protection against HIV-1. |
