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Ann Clin Trials Vaccines Res. 2017 | Volume 1 Issue 2
allied
academies
Global Vaccines & Vaccination Summit & B2B
November 01-02, 2017 | Toronto, Canada
O
ne of the most successful and enduring accomplishments
of mankind to date is the prevention or effective control
of many infectious diseases through the use of vaccines.
Most vaccines have been administered via the systemic
(intramuscular/intracutaneous/subcutaneous) route. Such
vaccines have resulted in significant decline in the disease
burden of systemic infections associated with blood stream
involvement, such as diphtheria, tetanus, pertussis, hemophilus
influenzae, mumps, measles, rubella, and in the complete
eradication of smallpox, Poliovirus type2 infection, and virtual
elimination of other poliovirus types in most parts of the
world. Systemic immunization has been highly effective in
inducing systemic innate and adaptive immune responses,
but limited or variable degree of immunity in the mucosal
sites. Most human infections are acquired via the external
mucosal surfaces of the respiratory, gastrointestinal, urogenital
tracts. Human and other mammalian mucosal surfaces are in
continuous contact with external environment and exposed to
an overwhelming spectrum of microorganisms, dietary agents
and other environmental macromolecules. It is estimated
that the human intestinal mucosa alone contains > bacterial
organisms representing as many as 2000 species, and over
virus -like particles/gm of feces, of nearly 1,000 viral species.
In addition to the bacteria and viruses, human mucosal
surfaces are the primary portals of entry and sites of initial
colonization with many fungi and parasitic agents. However,
pathogenic agents represent a very tiny fraction of the entire
mucosal microbial repertoire. The mucosal surfaces of the
human neonate begin to be colonized with components of
maternal microbiome shortly before, during the process of
birth and, subsequently within the first 2-3 weeks after birth
from maternal and other environmental exposures. Studies
over the past 5 decades have demonstrated an extensive and
intercommunicative network of innate and adaptive immune
mechanisms in the mucosa associated lymphoid tissue(MALT)
distributed in the gut (GALT), upper Respiratory and bronchial
epithelium (BALT), nose-nasopharynx-waldyers ring(NALT),
Sublingual tissue(SLT),Urogenital tissue and mammary glands,
and Skin(SALT). These lymphoid elements are collectively
referred as the common mucosal Immune system. There is
now increasing evidence to suggest that induction of protective
immune response in the specific mucosal portals of entry is
the most effective approach to regulate local colonization
and subsequent disease outcome. Currently available
mucosal vaccines include vaccines against, polioviruses,(live
attenuated- oral) rotavirus (live attenuated–oral)
influenza
virus
(live attenuated–nasal),
vibrio cholera
(inactivated-
oral) and
salmonella typhi
(live attenuated-oral). Several
other candidate mucosal vaccines are currently undergoing
evaluations in human trials. These include, enterotoxigenic
E.coli
(ETEC),
Shigella
,
Helicobacter
,
Campylobacter
,
Salmonella
paratyphi
, and
Norovirus
. The composition and the diversity
of mucosal microbiome have been shown to have a profound
influence on the induction of immune response and efficacy
of mucosally introduced vaccines, especially in tropics. Other
possible factors which influence the effectiveness of mucosal
vaccines include, methods delivery of the infant (vaginal vs
C-section), postnatal feeding practices, malnutrition and
carbohydrate consumption, use of antibiotics, and mucosal
inflammation. Currently, mucosally delivered vaccines comprise
of non- replicating whole organisms, synthetic peptides,
inactivated toxins, and recombinant subunit proteins. In order
to improve their immunogenicity and protective efficacy, the
use of adjuvants has been explored in several clinical trials.
These include, adjuvants which facilitate effective delivery of
vaccine antigens (liposomes, nanogels, oil-in-water emulsions);
adjuvants directed at targeting vaccine antigens to professional
antigen presenting cells (APC) (Virosomes). Finally, several
Pearay L Ogra
State University of New York, USA
Recent progress in human mucosal vaccine development: Role of mucosal
immunity and mucosal microbiome in the outcome of vaccine effectiveness