11-3-09 Vaccines 1. Describe the immune response induced upon successful vaccination.

A vaccine should produce two effects that enhance adaptive immunity: 1. induce neutralizing antibodies to prevent the pathogen from infecting cells. a. The affinity and amount of anti ody increases with repeated immuni!ations "i.e. a ooster induces a secondary response that is more rapid and generates a greater level of anti odies with higher affinity# $. upregulate cytotoxic (CD8) T cells to eliminate infected cells. a. %i&e ' cells( the )T% response similarly has oth specificity and memory The relative importance of humoral versus cell-mediated immunity depends on the pathogen. The vaccine acts y introducing antigens that are presented on A*)s( which go on to activate helper T cells. The helper Ts activate ' cells to ma&e anti odies A+, activates cytoto-ic T cells. . !hat are the advantages"disadvantages of the types of vaccines used today# Vaccines against viruses $ive attenuated virus In vitro( passed in culture from non-native host .enerally considered more useful as they mimic the natural disease process( causing long lasting immunity. /owever( they can e unsta le with the possi ility of reversion to virulence or reduction in potency. %ive attenuateds may e dangerous to the immunocompromised. 0-: 1123 vaccine( 4a in33 vaccine "no longer used#( yellow fever( Salmonella typhi Ty$1A( chic&enpo- "results in milder shingles#( rotavirus diarrhea( %nactivated vaccines 0-: 4al&33 vaccine 3112 vaccine can only e administered in a ies after maternal anti odies have waned. There is no evidence that it causes autism. 33Although live attenuated vaccines are considered 5the est6( the 4a in vaccine was discontinued to several cases of paralytic disease. The 4al& vaccine is used instead. 4al&: inactive virus7g. neutrali!ing anti ody prevents virus from entering )+4 4a in: live attenuated virus7gA prevents entry of virus through mucosa *olio has +8T een eradicated ecause it is often difficult to detect infection( and immunocompromised patients shed virus for years. Vaccines against acteria DTa& vaccine: inactivated to-ins "to-oids# for diphtheria( tetanus( and pertussis "whooping cough# Toxoids function in stimulating the production of neutralizing antibodies( which neutrali!e the micro ial to-ins Con'ugate vaccines ,eveloped as a result of understanding how T and B cells collaborate in an immune response

9sed for infants( who under two years of age cannot ma&e good T-independent anti ody responses )hemical con:ugation of acterial polysaccharides to proteins(a toxoid carrier) allows for peptide recognition y antigen-specific T cells( su se;uently invol&ing a protective 7g. response 0-: Haemophilus influenzae type ' "an important cause of serious childhood chest infections and meningitis#( Neisseria meningitides( and Streptococcus pneumoniae

5+ew6 vaccines (ubunit vaccines )omposed of the capsid or envelope protein of a virus< used when other vaccines are ineffective and cannot e manufactured 0-: hepatitis ' "can=t grow in culture#( /7V "too dangerous to use live#( herpes simple- "may ecome latent in ody for later reactivation#( influen!a "poorly effective and with side effects# )irus*li+e particles /*V: contains an %1 particle that can self-assem le to form virus-li&e particles with neutrali!ation anti ody epitopes &assive immunization 7mmediate ut temporary protection against pathogens and to-ins via transfer of antiserum 2epeated administration can lead to serum sic&ness "fever( vasculitis( nephritis( arthritis# Anaphyla-is can also occur if the recipient ecomes allergic to the foreign source 0-: anti-sna&e serums "horse and sheep serum are the usual sources#( one marrow transplants "7v7g# The transfer of maternal 7g. to the fetus is considered a form of passive immuni!ation Vaccines of the future /7V vaccine ,ifficult ecause /7V generates an adaptive immune response that contains the virus ut rarely if ever eliminates it. That=s ecause /7V has three uni;ue properties: 7nfects ),> T cells 2everse transcription ,ecoy envelope protein gp1$0 The goal is to increase concentration of !"# cytotoxic T cells( which can e accomplished y D,- vaccination ,+A vaccination involves in:ecting a nonreplicating bacterial plasmid encoding viral protein intramuscularly. This will generate anti odies and )T%s to the viral protein that protects from challenge with live virus. Any other vaccines aimed at increasing ),? T cell levels must ta&e into account@ The 1/)s of recipient populations And the strains of /7V to which they are e-posed

Another method of com ating /7V would e to have a vaccine that generates neutrali!ing anti odies( ut this has not een successful 2everse vaccinology 7nvolves protease digestion of whole acteria to 5shave6 protruding protein domains on the surface *rotein domains are separated y mass spec( 7,ed( then vaccinated into mice for testing ,elivery 7n:ection is not the most effective way of stimulating an appropriate immune response ecause it does not mimic the usual route of entry for the ma:ority of pathogens. 1ucosal vaccines "oral or nasal# are important developments ,+A vaccines can e coated on minute metal particles which can e administered on a allistic gun "good for mass immuni!ation#

.. !hat fundamental principles are useful to +no/ /hen designing a ne/ vaccine# An effective vaccine must e: (afe: not cause illness and death. 7t must also e perceived to e safe y the pu lic and the medical profession &rotective /ave sustained protection for several years against illness Cheap 0eat*stable 1asy to administer 2e/ side effects 3. !hy is the timing of immunization in children important# 7nfants have transiently low 7g levels which can lead to suscepti ility to disease. At irth( the neonate has high levels of 7g. that had een passively transferred from the mother. The 7g. level declines steadily after irth( efore the infant can produce ade;uate amounts of 7g1( 7g. and 7gA. Thus( there is a window of time where there is higher suscepti ility to disease. 8n the other hand( the maternal anti odies can inhi it effective immuni!ation. Vaccines li&e 112 can only e administered after maternal anti odies have waned. 1oreover( children under $ years of age cannot generate a good T-independent anti ody response "in other words( helper T cells must e involved to help present antigens to naAve ' cells#. A con'ugated vaccine is composed of chemically con$ugated bacterial polysaccharides to proteins. The proteins can then e recogni!ed y antigen-specific T cells. Additional notes: 0erd immunity: immunity possessed y an entire population when a ma:or segment of that population is immune to the agent

/erd immunity played a role in the eradication of smallpox. The first smallpo- vaccine was developed y 0dward Benner( who noted that dairymaids "4arah +elmes# who contracted cowpo- developed immunity to smallpo-. 7t turned out that cowpo- virus is antigenically related to smallpo- virus and induces immunity to smallpo- without causing severe disease. 1assive immuni!ation efforts led to eradication in 19?0. )owpo- virus is no longer used. 2ather( vaccinia virus is used for modern vaccines. %ive smallpo- virus still e-ist in the 94 and 2ussia.