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Future Needs for Vaccines: Influenza, Malaria, Tuberculosis, HIV

by Peter Delves, PhD
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    00:01 There is a need for both new vaccines and improved versions of existing vaccines.

    00:09 For example, better vaccines against influenza, malaria, TB, and we still desperately need a vaccine against HIV.

    00:21 The vaccines against influenza are perfectly good.

    00:25 The problem is that the influenza virus is changing all the time by mutations.

    00:31 And therefore the vaccine needs to be administered every year to provide protection against new variants of the virus.

    00:40 The influenza virus can undergo two types of genetic change.

    00:44 We call them antigenic drift and antigenic shift.

    00:49 Antigenic drift refers to point mutation.

    00:54 The neuraminidase and hemaglutinin antigens in the influenza virus can undergo point mutations.

    01:03 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.

    01:12 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.

    01:23 This will mean that people exposed to the previous version will have partial immunity but not full immunity to this new variant.

    01:33 In contrast, antigenic shift involves the exchange of genetic material.

    01:40 So for example, there may be exchange between a human influenza virus and an avian influenza virus.

    01:47 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.

    02:16 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.

    02:31 They’re distributed and then individuals are vaccinated.

    02:37 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.

    02:57 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.

    04:20 It targets the pre-erythrocyte stage of the parasite.

    04:25 In this trial, a large number of infants and young children were vaccinated.

    04:31 And the overall efficacy against severe malaria in 5-17 month old children was 32.2%.

    04:41 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.

    05:04 It is used in countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease.

    05:13 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.

    05:29 It is considered only for children who have a negative tuberculin skin test and a high risk from exposure.

    05:38 For example, if they are continually exposed to isoniazid and to rifampin resistant M. TB.

    05:48 Healthcare workers who are routinely exposed to drug resistant M. TB are also vaccinated.

    05:59 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.

    06:20 Broadly neutralizing antibodies have been identified in a very small number of people living with HIV.

    06:26 And intravenous infusion of such antibodies is entering clinical trials.

    06:34 There’s no vaccine tested in clinical trials so far that has been sufficiently successful.

    06:41 The only hint of any success whatsoever was a trial carried out in Thailand in 2009.

    06:49 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.

    07:18 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.

    07:30 Effective vaccines for HIV, TB and malaria.

    07:36 A broadly specific influenza vaccine so that individuals don’t need to be vaccinated every single year.

    07:43 Therapeutic vaccines for those already exposed to pathogens; so a hepatitis vaccine, HIV vaccine and vaccines against cancer.

    07:55 And also there is a need for vaccines against a number of parasitic diseases.


    About the Lecture

    The lecture Future Needs for Vaccines: Influenza, Malaria, Tuberculosis, HIV by Peter Delves, PhD is from the course Vaccine Immunology. It contains the following chapters:

    • Future Needs for Vaccines
    • Influenza Vaccines
    • Malaria Vaccines
    • Tuberculosis Vaccines
    • HIV Vaccines

    Included Quiz Questions

    1. 3
    2. 1
    3. 2
    4. 5
    5. 6
    1. The pre-erythrocyte stage
    2. In subcutaneous tissue
    3. The erythrocyte stage
    4. In infected erythrocytes
    5. In blood plasma
    1. Children and healthcare workers at high risk of exposure to drug-resistant strains
    2. Healthcare workers in the US
    3. Everyone in the US
    4. Adults who have been exposed to drug-resistant strains
    5. Children who have had miliary disease in the past
    1. Tetanus
    2. HIV
    3. Parasitic infections
    4. Hepatitis
    5. TB

    Author of lecture Future Needs for Vaccines: Influenza, Malaria, Tuberculosis, HIV

     Peter Delves, PhD

    Peter Delves, PhD


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