Recent advances in vaccine development The document discusses recent advances in vaccine development technologies, including DNA vaccines, transgenic plant vaccines, sugar glass vaccines, skin patch vaccines, and combination vaccines. DNA vaccines work by delivering pathogen genes into the body to produce antigens and elicit an immune response. Transgenic plant vaccines produce antigens in edible plants that are eaten to deliver the vaccine. Sugar glass vaccines preserve vaccine potency by immobilizing antigens in a sugar glass matrix. Skin patch vaccines target skin immune cells for vaccination. Combination vaccines provide protection against multiple diseases in a single vaccine dose. The document also discusses challenges in vaccine development like inadequate preclinical data, lack of information on target populations, high development costs, and antigenic variation requiring constant vaccine

1. Recent advances in vaccine development
Presented by – AMIT P. TIWARI

2. Vaccinology: Traditional Technologies
• In the pre-recombinant DNA era, most of the vaccines were developed by a
process of trial and error in animal and human experiments.
• In tropical countries, vaccines are not available for many diseases and the old
conventional and traditional approaches to vaccination are not successful.
• The reasons for failure are inability to grow the organisms and complexity of
the life cycle of organism.
• The principal aim of vaccination is to prime the immune system to destroy
specific disease causing pathogen before the pathogen can multiply enough to
produce the disease or symptoms.

3. Vaccinology: Traditional Technologies
• The priming can be achieved by using killed or weakened (attenuated)
version of pathogen or of some piece of the pathogen (subunit).
• The immune system by detecting the presence of organism in vaccine
behaves as if the body was under attack and mobilizes all its defense forces
to destroy the invader.
• The immune system also leads to the creation of memory cells, which
remain on alert in future attacks with the same pathogen.

4. Vaccinology: Traditional Technologies
• Some of the traditional vaccines, which contain killed pathogens, give rise to primarily
humoral response and do not activate killer T cells.
• Such responses are ineffective against many microorganisms that infiltrate cells.
• Attenuated live vaccines, usually viruses, do enter cells and make antigens that are
displayed by the inoculated cells.
• They thus spur attack by killer T lymphocytes as well as by antibodies. That dual
activity is essential for blocking infection by many viruses and for ensuring immunity.
• Life long immunity is generally conferred by live vaccines such as measles, mumps,
rubella and small pox vaccines.

5. Vaccinology: Newer Technologies
a) DNA Vaccines
• The most recent development in vaccinology is immunization with polynucleotides
or genetic immunization or DNA immunization, which was discovered by chance
when plasmids carrying a gene from influenza virus could be used to immunize mice
and protect them from a lethal viral dose
• The DNA vaccines induce immune response to viruses, bacteria, fungi and parasite
and response was seen in birds, chimpanzees, cows, monkeys, mice, guinea pig and
in many other animals.

6. DNA Vaccines
• Consist of plasmids-small rings of double stranded DNA derived from a bacterium
(like Escherichia coli) but unable to produce infection.
• One or more genes are isolated from disease causing pathogen and inserted into
plasmids and delivered by injection or gene gun into muscle.
• The foreign genes express proteins (antigen) that elicit humoral and cellular
immunity.
• The immunologists were excited by the ability of DNA to elicit a broad immune
response of not only humoral immunity (antibodies) but also cell mediated immunity
especially cytotoxic T cells (CTL)

7. Questions on safety of DNA vaccines
• a) Could the DNA vaccine integrate into host's own DNA?;
• b) DNA vaccines stays for a long time in host cells and could this prolonged
stimulation cause chronic inflammation or auto-immune reaction? And
• c) Could antibodies to a DNA vaccine recognize the vaccine recipient's own DNA and
cause autoimmune disease?

8. Advantages of DNA vaccines
• Safe and no risk of disease
• Broad range of immune response
• Antigen confirmation normal
• No injection site reaction
• Duration of immunity long
• Simple, cheap to produce
• Multiple vaccines can be administered simultaneously
• Neonatal immunization in presence of maternal antibody possible
• Various delivery methods available

9. Pathogens
• About 40 DNA vaccines against 30 different conditions are under progress and five
vaccines against hepatitis-B, herpes Simplex, HIV, influenza and malaria are being
used in human trials. They are in early stage in examining their immunogenicity and
safety.
• Pathogens for which DNA vaccines provokes immune response in animal models
• Viruses :Rabies, Rota virus, Measles, Rubella, Dengue, Ebola, Simian HIV, Herpes,
Influenza, Japanese encephalitis, Cytomegalo virus, Coxsackie virus, Foot and mouth
disease virus, Hanta virus, Canine distemper virus, Canine parvovirus
• Bacteria: Mycoplasma, Shigella, Chlamydia, Clostridium tetani (Tetanus),
Mycobacterium tuberculosis (TB), Bacillus anthracis (Anthrax), Borrelia burgdonferi
(Lyme disease), Enterotoxigenic E. coli, Mycobacterium sp.
• Fungi : Coccidioides immitis
• Parasites: Leishmania, Plasmodia (Malaria), Schistosomes, Onchocerca (River
blindness), Taenia crassiceps, Trypanosoma cruzi

10. B) Transgenic Plant Vaccines
• They are also known as edible vaccines.
• The concept of expressing the viral epitopes and subunits of bacterial toxins in
transgenic plants have been successfully shown in various studies and with edible
vaccines, the plants not only manufacture the antigens but also deliver it into the host.
• The foreign DNA inserted in the genomes of plants-notably, tobacco and petunia
(Broglie, 1984), successfully expressed the foreign DNA and using this approach
vaccines were produced in the edible parts of plants, which could be eaten when
inoculations were needed

11. Transgenic Plant Vaccines
• Some of the foods under study are alternatively to injectable vaccines include
bananas, potatoes and tomatoes as well as rice, lettuce, wheat, com and soybean.
• The edible vaccines are safe, lack contamination with animal pathogens, require
minimal downstream processing, easy to administer and do not require
refrigeration and syringes.
• The plants can be grown locally, cheaply and they act as natural bioreactors.
• The results of these studies are encouraging.
• The day is not far off when children are immunized by munching on foods
instead of shots.

12. C) Sugar Glass Vaccines
• The saturated solution of trehalose, on cooling, slides smoothly from a liquid to a viscous and
ultimately to a solid glass like state called "Sugar Glass".
• The glass dissolves on contact with water and releases its contents.
• In trehalose formulations, the vaccine appears to suffer no detectable loss of potency after long
periods of exposure to heat or freezing.
• The sugar glass immobilizes, preserves and protects protein and other molecules from solutions.
• The measles vaccine losses over 90% of potency after two months at room temperature and shows
no loss of potency as a trehalose powder under the same conditions.
• The influenza and tetanus vaccines did not show any adverse effect on potency even after storing
at below -70℃ for nine months.
• Pertussis antigen retained its original activity for three months at 37℃. However, the application
of this technology has limited interest for vaccine producers.

13. D) Skin Patch Vaccines
• Superficial layers of skin are the perfect gateway to many key areas of immune system
known as transcutaneous immunization.
• This technology appears to target highly accessible antigen presenting cells in the skin
that can be exploited for a variety of immune outcomes.
• Cholera toxin (CT) is a powerful stimulator of the immune system and human volunteers
have been vaccinated by skin patch method.
• The results are encouraging and the CT mixed with vaccinating antigens have shown
cellular and antibody mediated responses.
• This technology is being used to develop vaccines against viral and bacterial infections.

14. E) Combination of Vaccines
• Combination of vaccines, developed and exploited in 20th century, can be both live
[Measles-Mumps-Rubella (MMR), Polio] or inactivated/killed subunit [Diphtheria-
Tetanus-Pertussis (DTP),. Hepatitis B (HB), Haemophilus influenza type b (Hib)].
• Presently, the main thrust in the development of new combined vaccines has been
DTP based multi disease combination for pediatric use.
• Combined vaccines, if developed successfully, can reduce the infections during the
first two years of life from 15 to 5.
• The combinations in use are combined Pneumococcal and Meningococcal vaccines,
DTP-Hib, DTP-IPY, DTPHB, MMR and attenuated Varicella vaccine (MMRV),
hepatitis A and B, DTP-HB-Hib and DTPHB-IPV.

15. Advantages of Combined Vaccines
• Low cost
• Easy delivery
• Less number of visits
• Less injections for immunization

16. Disadvantages of combined vaccine
• Reduced immunogenicity (interference)
• Increased side effects
• Each combination needs to be tested extensively before licensing.

17. F) Immunomodulation Delivery
• Modulation of the immune responses is now possible with cytokines and new
adjuvants.
• The use of immunomodulators offers the hope of developing vaccines against
infections that do not stimulate strong natural immunity.
• In coming years this approach will be used against chronic infections like hepatitis B
for developing therapeutic vaccines called Pharmaccines.
• This approach could also be used in conditions where there is malfunction of the
immune system like allergies and autoimmune diseases.

18. Challenges faced
• Vaccine development has played a hugely important role in combating infectious
disease.
• Despite this success, there is still a great need for new vaccines and these are
emerging far more slowly than expected.
• A large number of vaccines were simply formulated with Aluminium Hydroxide as
the adjuvant and are administered by injection.

19. Problem Actions required
Inadequate preclinical data and lack of detailed
information on protective correlates of immunity
contribute to product failure in clinical trials
Development of more relevant animal models; more human samples
to be collected and analysed; increased use of experimental human
challenge infections
Lack of information on the infectious exposures of
intended vaccine recipients
More human samples to be collected and analysed
Vaccines are to be used in populations with less-
responsive immune systems
Gain a greater understanding of the mechanisms of action of currently
used adjuvants; development of vaccine delivery systems specifically
for use in immunocompromised populations
Inadequate access to vaccines in poorer countries,
especially those for use against tropical diseases
More tiered pricing strategies; facilitate the development of vaccines
in developing countries
Antigenic variation requires constant updating of vaccine
formulations
Seek conserved antigens; monitor genetic variation of infectious
organisms in the community
High costs of vaccine development result in premature
abandonment of potentially useful products
More investment in vaccine research

20. THANK YOU!