1. Next-Generation Vaccine Delivery
RNCOS Insight
Effective vaccine development and delivery is a never-ending challenge in the global biotechnology
industry. From traditional methods to efficient systems, the vaccine industry has evolved greatly but
there is still some time before it can be safely called – The Next-Generation for Vaccines
2. Next-Generation Vaccine Delivery - RNCOS Insight
There is robust ongoing research
and development for more efficient vaccine delivery
systems that could dynamically change the way
vaccines are administered.
• There are several kinds of vaccines
being developed in the market and
research is aiming to overcome
limitations posed by traditional
techniques.
• Novel vaccine delivery systems will
address both basic vaccine
administration issues while improving
dose efficacy.
• Nanotechnology in particular carries
great hope for high-throughput vaccine
delivery systems.
• The parallelism between market players
and researchers will largely determine
the reshaping of the vaccine industry.
Effective vaccine development and delivery is a never-ending
challenge in the global biotechnology industry. From traditional
methods to efficient systems, the vaccine industry has evolved
greatly and but there is still some time before it can be safely
called – The Next-Generation for Vaccines.
Traditional vaccine delivery has limitations which are now being
challenged by new technologies with the aim to address basic
issues such as lack of trained personnel for administration,
storage issues, cold chain problem, variability in the follow of
norms such as reuse, disposal, expiry of products etc. Research is
also focusing on technical aspects of increasing effectiveness of
vaccine by enhancing immune response, reducing the number of
doses and improving the scalability and manufacture of vaccines.
The market today is reveling in a phase of novel vaccine
development and delivery systems which allow presentation of
antigens that activate an entire spectrum of immune response in
the right composition besides providing a wide range of vaccines
to choose from.
Current Types
Historically, there have been several vaccine types being
developed based on the fundamental principle of microbe
infecting the person. Broadly vaccines can be classified as live
attenuated, inactivated, subunit, toxoid, conjugate, DNA and
recombinant vector vaccines.
3. Vaccine Type
Live
attenuated
vaccine
Inactivated
vaccine
Subunit
vaccine
Toxoid
vaccine
Conjugate
vaccines
DNA
vaccines
Recombinant
vector
vaccines
Figure 1: Classification of Vaccines by Type
Live, attenuated vaccines are relatively easy to
create for certain viruses but difficult for
bacteria and also pose the threat of getting
mutated and turning virulent. Inactivated
vaccines on the other hand offer a more stable
and safer option than live vaccines. However,
these vaccines have a limitation of stimulating a
weaker immune system response than live
vaccines, hence requiring additional doses. Sub-
unit vaccines, although causing lesser adverse
events, have led to a common belief of them
being insufficiently immunogenic apart from
having a cumbersome process of identifying key
sub unit. Toxoid vaccines are effective solutions
but are limited to cases where toxoid
production is the main cause of disease.
Conjugate vaccines are expected to overcome
most of the problems inherent in the
polysaccharide vaccine. DNA Vaccines and
recombinant vector vaccine are still in
experimental stages and have revealed some
very promising outcomes. However, both need
more research to gain sufficient understanding
on their overall effects.
Current Vaccine Delivery Routes
The most common vaccine delivery route has
been parenteral, based on needle injection that
spreads the vaccine through body fluids to
various organs and induces antibody response.
Parenteral administration can be done in an
intra-muscular and a subcutaneous fashion.
Currently licensed formulations such as gardasil
for HPV, hepatitis A, rabies and influenza
vaccines are prominent examples of intra-
muscular delivery while MMR, meningococcal,
Source: NIAID
Last Updated April 03, 2012
- Contains live
and weakened
strains of
microbes.
- Trains immune
system to elicit
strong cellular
and antibody
response on
actual microbial
attack.
- Examples
include vaccines
for chicken pox,
measles etc.
- Produced by
killing the
disease-causing
microbe with
chemicals, heat,
or radiation.
- Upon
administration,
activated
antibody already
present in blood
starts body’s
defense.
- Examples
include vaccines
for influenza,
rabies etc.
- Contains the
specific part of
the antigen,
instead of the
entire microbe,
that can best
elicit immune
response.
- Subunit vaccines
can contain
anywhere from 1
to 20 or more
antigens
- Examples
include
Recombinant
Hepatitis B
Vaccine amongst
others.
- Used when
disease is caused
by harmful toxins
known as toxoids
released by
bacteria.
- Contains the
inactivated toxoid
against which the
body gets trained
to develop
immune
response.
- Examples
include vaccines
against diphtheria
and tetanus.
- A special type of
subunit vaccine
that contains
recognizable
antigens or
toxoids from a
microbe linked to
the bacterial
polysaccharides.
- Linkage helps
immature
immune system
react to
polysaccharide
coatings.
- Examples
include
Haemophilus
influenzae type B
(Hib) vaccine.
- Contains
segments of key
microbial genes
that cause
infection
- Some cells take
up the antigen -
producing DNA
and train body to
elicit immune
response.
- Vaccine in
experimental
stages
- Use attenuated
virus or
bacterium known
as vector, to
introduce
microbial DNA to
cells of the body.
- Some cells take
up the antigen -
producing DNA
and train body to
elicit immune
response.
- Vaccine in
experimental
stages
4. Researchers and industry players
are striking novelty in vaccines
towards needle- free delivery.
Alternate routes of vaccine
delivery remains a quest with
research proving efficacy of
alternate routes such as
sublingual, intradermal etc.
Aerosol immunizations and
inhalable vaccines to challenge
traditional vaccine delivery
systems.
and varicella vaccines are delivered
subcutaneously.
Non-invasive vaccine delivery routes have also
emerged successful in recent times. Mucosal
vaccines in particular, comprising of oral, nasal,
vaginal and rectal vaccines are gaining
presence. Mucosal surfaces are enormous
surface areas that are prone to infection by
pathogens and immune responses can be
effectively induced by administrating vaccines
onto such mucosal surfaces. Sabin oral polio
and the rotavirus vaccines are the two
currently licensed oral vaccines available while
live FluMist against influenza is the only nasal
delivery option available. Vaginal and rectal
vaccination routes, though still under research,
will offer tremendous results to overcome
sexually transmitted diseases.
Research is being conducted to discover
alternate routes of vaccine delivery that aids in
generating more specific and heightened
response to eliminate pathogens at the entry
point itself.
Novelty in Vaccine Delivery - The New
Paradigm
Delivery systems have experienced
modifications from traditional syringes to
throughput systems of multi-dose needle-free
injectors and prefilled devices.
Needle free delivery has become an urgent
priority in this regard and scientists are also
intensely studying alternate and modified
routes of vaccine delivery such as sublingual
and intradermal routes amongst others.
Researchers recently identified an efficient
sublingual route for delivering vaccines capable
of inducing mucosal as well as systemic immune
responses against a lethal genital
papillomavirus.
Aerosol Immunization and inhalable vaccines
are aiding to eliminate traditional limitations
and have been implemented in diseases such as
measles and influenza respectively. Delivery
systems such as Jet nebulizers and Ultrasonic
nebulizer are being evaluated to control doses
of vaccines delivered in such cases.
Microneedle vaccine delivery is a new concept
in vaccine administration that has already
shown promising outcomes. These delivery
systems are basically patches containing
micron-scale needles that carry skin-dissolvable
vaccines. Aimed at reducing pain of syringes
and simplifying immunization, these systems
have the potential to allow self-administration
of vaccine during pandemics and greatly
disinvolve large-scale immunization programs in
developing nations. In a recent development,
researchers from the Georgia Institute of
Technology and the Centers for Disease Control
and Prevention demonstrated that the measles
vaccine remains effective for at least 30 days
when placed onto microneedles.
Nanotechnology is one field that has
revolutionized the development of novel
vaccine delivery systems. Nanoparticles have
achieved such high standards of specificity by
enabling the delivery of antigens to not only the
desired site but to the relevant antigen
presenting cells. Innovations such as the
needle-free nanopatch vaccine delivery system
has thousands of small projections to deliver
vaccines to abundant immune cells in the skin,
doing away with needles plunged into muscle
where fewer immune cells are present.
5. Miniaturization has made its way
majorly into vaccine delivery.
Microneedle delivery, consisting
of micron-scale needles on skin
patches is showing promising
outcomes for vaccine
administration.
Nanotechnology is being actively
explored especially for nano-scale
skin patches.
Unique techniques are also being
explored such as the use of pollen
grains for delivering oral vaccines.
Technology too is in no way behind to create
robust delivery systems. PRINT (Particle
Replication in Non-wetting Templates)
technology is currently gaining highlight as a
powerful nano-molding technique that enables
the fabrication of particles with precise control
over the shape, size, composition, and surface
functionality.
Apart from this, scientists are on a constant
mission to extract more interesting and capable
vaccine delivery systems. For example, A
research project at the U.S. Defense Advanced
Research Projects Agency (DARPA) is looking at
turning pollen grains into a delivery system for
oral vaccines for creating a vaccine that is easy
to transport and easy to take and requiring no
specialist medical training. This is expected to
be particularly important for troops deployed in
remote areas and for people living in areas
where medical support is slacking.
Next-Generation Vaccine Delivery Systems
- Revolution Impending
RNCOS feels that the way vaccines will be
administered in the future would solely depend
on the research outcomes of studies being
conducted. However, it can be said with
certainty that the Global vaccine industry in
near times will witness a dynamic shift from a
syringe and a vial to tech-savvy gadgets and
miniaturized delivery systems. Efficient vaccine
delivery systems and scale ups would mean
faster eradication of diseases and an era of
equitable health. Achieving this, however, will
be at the discretion of market players and
manufacturers who ideally should be in
absolute coherence with ongoing research to
convert R&D into marketable products.
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VARTIKA SEHGAL
Sr. Research Specialist
RNCOS
E mail: vartika.sehgal@rncos.com
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