vaccine assignment final

8/11/2019 Vaccine Assignment Final

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London School of Hygiene & Tropical Medicine

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Is it theoretically possible to generate a vaccine that is more

efective at inducing protective immunity than the inection

itself?

Immunity as evolutionary contest between pathogen and hostThe ecological interaction between infectious pathogen and host is one where

the pathogens evolutionary goal is continued reproduction. Many infections result in

complete elimination of pathogen with subsequent lifelong immunity against

reinfection. Evolutionary considerations may suggest that natural immunity has been

optimized over long periods and articial vaccines are likely to be inferior. The second

category includes diseases and vaccines under consideration in this essay namely

those in which the immune system is either unable to fully eliminate primary

infection or is unable to prevent subsequent reinfection of the same species of

infectious agent through immunological memory. This limitation of protective

immunity allows a theoretical possibility of designing a vaccine to provide greater

e!cacy at inducing protective immunity than natural infection.

Epidemiological evidence

"ssessing natural immunity compared to vaccine#mediated immunity is by nomeans simple. "side from challenge e$periments which are an ethical quagmire the

ne$t best estimates would come from epidemiological surveys. True estimates would

require large samples including adequate unvaccinated cases problematic for diseases

with widespread vaccine coverage in order to pick up rare cases of actual infection.

%urther detailed lifelong histories together with laboratory conrmed status of past

infection &including ideally molecular typing and serological correlates' would be

necessary to compare against vaccination histories if possible along with e$posure

histories. %or many diseases based on limited evidence there is a widespread

understanding that natural immunity is better than vaccine#mediated immunity (.

)nfortunately this is dependent on surveillance for repeat infections which is of a

di*erent quality in the pre#vaccination era compared to the present.

(+%requently "sked ,uestions # -accination # Ministre de /a 0ant1 et 2es 0ervices 0ociau$

https344www.msss.gouv.qc.ca4su5ets4santepub4vaccination4inde$.php6foire7au$7questions7en8q(9

:accessed ;< March =? +@eneral -accine 0afety Aoncerns B The Ahildrens Cospital of

Dhiladelphia http344www.chop.edu4service4vaccine#education#center4vaccine#safety4general#safety#

concerns.html8natural#infection :accessed ;< March =.


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Tetanus may provide the strongest e$ample for the possibility of better vaccine#

mediated immunity than natural immunity using epidemiological evidence while

comparing to a well#described e$ample of where natural immunity is usually said to

be better than vaccine#mediated immunity namely varicella. %or tetanus received

wisdom is that infection does not confer immunityF =. 0eries of repeated infections

have been reported;. Grreversible binding and rapid sequestration of the tetanus to$in

tetanospasmin into neurons may be responsible for the short e$posure of the to$in to

the immune system and thus minimizing time for generation of an adaptive immune

response. Together with the small doses required for a severe oHten fatal clinical

course few people develop antibodies as serosurveys in non#immunized populations

have shown9. Gn contrast the formaldehyde treated tetanus to$oid has a virtually

(


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demonstrates the very high rate of natural immunity. Gn contrast clinical e!cacy of

the varicella vaccine has been reported in a meta#analysis at Q9.LI &LI AG 99#(


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Th+ vs Th, responses

Xne classic e$ample of a pathogen biasing the TC(3TC= response ratio is in

leishmaniasis where di*use cutaneous leishmaniasis is one manifestation of a bias to

a A29 &Th=' dominated response with a lack of e!cient A2Q#mediated &Th(' killing of

parasites. Drotective immunity is thus limited in this more chronic form of infection.

"ttempts have been made to induce a Th( bias in the response when using vaccine

approaches including live attenuated killed and antigen#based methods by utilising

WA@ as an ad5uvant to enhance A2Q &ie TC(' response(


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antigen ( &/0"#(' the only P falciparumantigen e$pressed e$clusively by hepatocytes in

vaccination strategies by presenting it outside the tolerogenic environment of the

liver in order to stimulate the immune system into acting against liver#stage parasites

over and above the level of protective immunity generated by natural infection (L.

.ranuloma formation

Xrganisms may subvert natural protective immunity through stimulating

immunopathologic responses that serve to evade host defences. @ranuloma formation

by pathogens in the)ycobacterium tuberculosis&)tb' comple$ demonstrates this. )pon

initial infection inZammatory reaction oHten leads to a granuloma containing

dormant mycobacteria that are inaccessible to elimination by the immune system(N.Gt

can be conceived that vaccines leading to sterile eradication of )tbcan be designed

that overcome the suboptimal natural immunity leading to latent infection. Vaufmann

suggests a vaccine strategy of stimulating di*erent T cell populations that can in

concert eliminate latent)tb3 chemoattractant Th(O cells Th( cells that activate

macrophages cytoto$ic A2Q T cells that attack intracellular )tb and antibodies to

opsonize released)tb(O.

Host life stage-dependent immune status

/elative infantile immunode$iciency

" few infections are prominent in neonates and infants among them

0aemophilus in$luen*aetype W &0ib' which is encapsulated and for which immunity is

dependent on a thymus#independent polysaccharide antigen (Q. )nder = years of age

the immune system is not su!ciently matured to naturally resist invasive infection by

0ib thus causing high rates of morbidity and mortality in this age group(. The recent

(9Gan S. Arispe and others +Aellular and Molecular Mechanisms of /iver Tolerance Immunological

/evie's =(; &=


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use of a con5ugated vaccine &with diphtheria or tetanus to$oid' enhances

immunogenicity in this age group over that of natural infection leading to protection

against invasive disease=


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salivary antigens enhancing protective immunity over and above that of natural

infection=N.

Tissue-speci$ic life-stages

0chistosomes infect humans via the skin as cercarial larvae transiting throughthe skin as schistosomlae before maturing to adult worms with associated

immunopathology. epeated infections are common which indicates that adaptive

immunity against larval forms is not e*ective. Xne mechanism by which cercariae

avoid stimulating the immune system is by secretion of immune modulators

including prostaglandins which inhibit antigen#presentation by /angerhans cells in

the skin=O.The increased e!cacy of irradiated cercariae in inducing protective

immune in mouse models=Qdemonstrates how articial vaccine formulations focusing

on particular parasite life#stages may improve on natural immunity.

ConclusionThis essays aims to demonstrate that not only is it theoretically possible but

given denitional constraints vaccine#mediated immunity has already surpassed

natural immunity in a few cases by epidemiologic and immunologic criteria. Woth

clinical endpoints and immune correlates such as seroconversion have been used in

the discussion. %urther theoretical e$tensions to the principle have been proposedwithin a typology of compromised natural immune responses and suggestions of

potential vaccine strategies made.

=N/ukasz Vedzierski +/eishmaniasis -accine3 Uhere "re Ue Today6Journal of .lobal Infectious

iseases = &=


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References"bendroth "llison and "nn M. "rvin +Gmmune Evasion as a Dathogenic Mechanism of

-aricella Yoster -irus %eminars in Immunology (; &=


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avindran a5esh 0udipta Whowmick "mrita 2as and Sahid "li +Aomparison of WA@ MD/

and Aationic /iposome "d5uvant 0ystems in /eishmanial "ntigen -accine %ormulations

against Murine -isceral /eishmaniasis B)! )icrobiology (< &=


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vaccine assignment final

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