Active Passive Killed live or attenuated Transfer of performed organism injected which can antibodies induce immune response Long term Short term Immune system plays role No role of immune system Ex-Hepatitis B vaccine Ex- diptheriaDiphtheria-pertussis(acellular)- Hepatitis A &B tetanus (DPaT) MeaslesInactivated (Salk) polio vaccine Rabies (IPV)Measles-mumps-rubella (MMR) combined vaccineHaemophilus influenzae (Hib) vaccine
A vaccine is a biologicalpreparation that improvesimmunity to a particulardisease. A vaccine typicallycontains an agent thatresembles a disease-causingmicroorganism, and is oftenmade from weakened orkilled forms of the microbeor its toxins. Vaccine is a form of Activeimmunization
Edward Jenner-The term vaccine derives from Edward Jenner’s 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox. Louis Pasteur- generalized Jenners idea by developing a rabies vaccine, and in the nineteenth century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.
The Mechanismof a Vaccine In an idealscenario, whenever avaccine is firstadministered, it isphagocytized by anantigen presenting cell(APC). Recent research suggestthat it is particularlyimportant that the vaccinebe taken up by a dendriticcell. This is because dendriticcells play a key role inactivating T cells, whichbecome helper T cells (Thcells).
From there, the activatedTh cells goes on to activatemature B-cells. These activated B-cellsdivides into two celltypes, antibody-producingplasma cells and, mostimportantly, memory Bcells. Memory T-cells are alsoestablished, however, theyusually have a shorter half-life than memory Bcells, thus, they play only aminor role in long-termimmunity. Usually, there are nocytotoxic T-cells formedwhenever the bodyresponds to a vaccine.
PotentialShortcomingsof Vaccines In some rare cases, avaccine may directlyactivate a B cell, withoutstimulation from Th cells. Such antigens areknown as T-independent(TI) antigens. The problem with sucha response is that onlyIg-M antibodies areproduced and there areno memory cellsestablished. Thus, such a vaccinewill be useless againstestablishing immunity.
Killed/InactivatedSome vaccines containkilled, but previouslyvirulent, micro-organisms thathave been destroyed withchemicals, heat, radioactivity orantibiotics.Examples are the influenzavaccine, choleravaccine, bubonic plaguevaccine, polio vaccine, hepatitisA vaccine, and rabies vaccine
HEAT CHEMICAL INACTIVATEDINACTIVATED Heat inactivation is Chemical inactivation generally unsatisfactory with formaldehyde or because it causes various alkylating extensive denaturation agents has been of proteins; thus, any successful. epitopes that depend on E.g.-Salk Polio vaccine higher orders of protein structure are likely to be altered significantly.
Microorganisms can be attenuated so that they lose their ability to cause significant disease (pathogenicity) but retain their capacity for transient growth within an inoculated host. Attenuation often can be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants that are better suited to growth in the abnormal culture conditions and are therefore less capable of growth in the natural host.
pathogenic bacteria and virus mutants are selare grown in abnormal culture -ected
Toxoid Some species ofbacterial produce whatis known as exotoxins. Toxoid are vaccineswhich consist ofexotoxins that have beeninactivated, either byheat or chemicals. These vaccines areintended to build animmunity against thetoxins, but notnecessarily the bacteriathat produce the toxins. Some examples arebotulinum antitoxin anddiphtheria antitoxin
Recombinant Clone the gene for majorvaccines/Surface surface antigen of hepatitismolecule virus(HBsAg) Express in yeast cellThe gene encodingany immunogenicprotein can be Recombinant yeast cells arecloned and grown in large fermentersexpressed inbacterial, yeast, or Yeast cellmammalian cellsusing Recombinant harvested, disrupted byDNA technology high pressureExample-HepatitisB vaccine Recombinant HBsAg released& purified Produce Ab’s
Recombinant vectorvaccineGenes that encodemajor antigens ofespecially virulentpathogens can beintroduced intoattenuated viruses orbacteria.The attenuatedorganism serves as avector, replicatingwithin the host andexpressing the geneproduct of the pathogen.Example -vacciniavector vaccine
DNA vaccines consist of plasmids that contains genes for certain types of antigens Plasmid DNA encoding antigenic proteins is injected directly into the muscle of the recipient. Muscle cells take up the DNA and the encoded protein antigen is expressed, leading to both a humoral antibody response and a cell mediated response The fact that muscle cells express low levels of class I MHC molecules and do not express costimulatory molecules suggests that local dendritic cells maybe crucial to the development of antigenic responses to DNAvaccines Gene gun can also be used for administration
DNA VACCINE NON DNA VACCINE encoded protein is expressed Artificial form in the host in its natural form induce both humoral and One type of immunity cell-mediated immunity No memory(only in cause prolonged expression of the antigen, which some cases) generates significant immunological memory. Refrigeration is not required Handling problem for the handling and storage of the plasmid DNA same plasmid vector can be Can’t be reused used for different vaccines
Synthetic peptide vaccines Contain immunodominant B-cell and T-cell epitopes. Works intra cellularly therefore effective in CTL response There are number of innovative techniques are being applied to develop multivalent vaccines that can present multiple copies of a given peptide or a mixture of peptides to the immune system-:
Solid matrix–antibodyantigen(SMAA) complexes Monoclonal antibodiesare attached to solidmatrixSaturate the antibodywith desired antigen.Complex formed can beused as vaccine Induce both HIR andCMI Particulate naturetherefore increasedimmunogenicityfacilitating phagocytosis
DetergentoDetergent +protein antigen ->1,2,3oMixing protein and detergent and thenremove detergent from micelleoThe individual proteins orientthemselves with their hydrophilicresidues toward the aqueousenvironment and the hydrophobicresidues at the centre so as to excludetheir interaction with the aqueousenvironment.1.ISCOM-Immunostimulatingcomplexes (ISCOMs) are lipid carriersprepared by mixing protein withdetergent and a glycoside called Quil A.2.Liposome-Liposomes containingprotein antigens are prepared by mixingthe proteins with a suspensionof phospholipids under conditions thatform vesicles bounded by a bilayer.
Examples-influenzavirus -measles virus -hepatitis B virus -HIVfuse with the plasmamembrane to deliver theantigenintracellularly, where itcan be processed by thecytosolic pathway andthus induce a cell-mediated response
Chimeric vaccines usually consist of attenuated viruses that have been engineered to carry antigens from multiple types of pathogens. For example, the yellow fever vaccine YF17D has been engineered to carry antigens from HIV, different types of bacteria, malaria, even cancer. The main adv.of a Chimeric vaccine is the establishment of immunity against several different diseases with one administration
There are three main vaccine manufacturing strategies: In-vivo In-vitro Chemical Synthesis Some vaccines can be produced using any one of the three methods while for other vaccines, only one method will work.
In-VivoIn in-vivomanufacturing, thevaccine is producedinside a living organism.Embryonated Chickeneggs are commonlyused, particularly inproducing flu vaccines.Vaccines, such as anti-idiotype, can also beproduced in labanimals, such as mice.There are even somespecies of plant, such asbananas, that have beengenetically engineered toproduce a vaccine.
In-Vitro Here, usingrecombinant DNAtechnology, vaccines canbe produced in yeastcultures, bacterialcultures, or cell cultures.Recombinantvaccines, such aschimeric vaccines, areproduced in this manor.Attenuatedvirus/bacteria vaccinescan also be producedthis way.
ChemicalSynthesis Here, instead of usingbiological systems toproduce a vaccine, avaccine can be producedin a lab. Vaccines that utilizesynthetic peptides aswell as conjugated lipidsand polysaccharides aremanufactured this way. Usually, this method isused in combinationwith either in-vivo or in-vitro production.
The primary risk associated with vaccines, especially vaccines that utilize live organisms, is that the vaccine itself causes illness. This Happened with the orally administered Sabin vaccine for polio, where some individuals became ill and, in rare cases, even spread the illness to other individuals who were not exposed to the vaccine. Another risk is that the vaccine may behave as a super antigen and over stimulate the immune system. Yet a third risk is that some individuals may have an allergic reaction to the vaccine, especially vaccines produced in Embryonated chicken eggs and in transgenic plants.