There is a need for both new vaccines and
improved versions of existing vaccines.
For example, better vaccines against influenza, malaria,
TB, and we still desperately need a vaccine against HIV.
The vaccines against
influenza are perfectly good.
The problem is that the influenza virus
is changing all the time by mutations.
And therefore the vaccine needs to be administered every
year to provide protection against new variants of the virus.
The influenza virus can undergo
two types of genetic change.
We call them antigenic
drift and antigenic shift.
Antigenic drift refers
to point mutation.
The neuraminidase and hemaglutinin antigens in
the influenza virus can undergo point mutations.
And as you can see in this diagram
with the little red dot; if you
look carefully there you’ll see a little red dot has appeared.
This is to indicate a point mutation
that will lead to a slight change in one
or other of those two antigens - the
neuraminidase or the hemaglutinin antigens.
This will mean that people exposed to the previous version will
have partial immunity but not full immunity to this new variant.
In contrast, antigenic shift involves
the exchange of genetic material.
So for example, there may be exchange between a
human influenza virus and an avian influenza virus.
This exchange of genetic material
creates a completely new strain
of human influenza virus to which hardly anybody is immune.
These new variants of the virus can then
sweep through the world and cause pandemics.
With the current annual vaccine for influenza, there
is a global surveillance for emerging strains.
The FDA advisory panel selects three strains, that is thought
will be the dominant strains for the coming winter season.
These are manufactured and tested.
They’re distributed and then
individuals are vaccinated.
However because this has to occur
every year, the time scale means
that there is insufficient vaccine to vaccinate everybody.
There is ongoing research for a universal influenza vaccine
based upon parts of the virus that just cannot change.
There are certain things in a virus that just can’t change -
the bits that bind to the cell surface receptors on cells.
If they change, the virus
can no longer infect cells.
So the hope is in the future, we
will have a influenza vaccine that is
able to protect against a much wider
number of variants of influenza.
But at the moment, because of the time scale
involved and the limited amount of vaccine that can
be produced prior to the winter season, only a
particular at risk groups are usually vaccinated.
So the elderly, people with diabetes and other
conditions that make them more prone to infection.
There is a real need for a malaria
vaccine and some progress is being made.
Malaria is caused by the Plasmodium protozoan
parasite, and there is a trial that has recently
been completed in Sub-Saharan Africa using a
particular vaccine that is called RTSS/AS01.
This comprises a portion of the circumsporozoite protein of
Plasmodium falciparum fused to a Hepatitis B surface antigen.
It targets the pre-erythrocyte
stage of the parasite.
In this trial, a large number of infants
and young children were vaccinated.
And the overall efficacy against severe
malaria in 5-17 month old children was 32.2%.
So by no means a perfect vaccine, but at least some progress
in towards the production of a effective malarial vaccine.
The BCG vaccine for tuberculosis is an attenuated live
Bacille Calmette Guerin strain of Mycobacterium bovis.
It is used in countries with a high prevalence of TB to
prevent childhood tuberculous meningitis and miliary disease.
It is not generally recommended in the USA due to a low
risk of infection with Mycobacterium tuberculosis and a
variable effectiveness against adult pulmonary TB and a
potential interference with the tuberculin skin test.
It is considered only for children who have a negative
tuberculin skin test and a high risk from exposure.
For example, if they are continually exposed
to isoniazid and to
rifampin resistant M. TB.
Healthcare workers who are routinely
exposed to drug resistant M. TB
are also vaccinated.
Regarding HIV vaccines, success requires identification
of immunogens and an immunization strategy that
induces broad and long lasting cytotoxic T-lymphocyte
immunity together with broadly neutralizing antibodies.
Broadly neutralizing antibodies have been identified
in a very small number of people living with HIV.
And intravenous infusion of such
antibodies is entering clinical trials.
There’s no vaccine tested in clinical trials
so far that has been sufficiently successful.
The only hint of any success whatsoever was
a trial carried out in Thailand in 2009.
This involved giving four priming injections of a recombinant
canarypox vector containing HIV gag, pol and env genes.
Two booster injections were
given with a recombinant gp120.
There was a limited protective
effect with an efficacy of 25-30%.
Currently there is a trial in South
Africa using a similar vaccine.
The future needs for vaccination are first of all,
the eradication of polio which has seemed so
close for a number of years now, and hopefully
will be achieved in the not too distant future.
Effective vaccines for
HIV, TB and malaria.
A broadly specific influenza vaccine so that individuals
don’t need to be vaccinated every single year.
Therapeutic vaccines for those already exposed to pathogens; so
a hepatitis vaccine, HIV vaccine and vaccines against cancer.
And also there is a need for vaccines
against a number of parasitic diseases.