vaccines/vaccine formulations Flashcards
(28 cards)
what is a vaccine
a preparation of a killed microorganism/living attenuated organism that is administered to produce/artificially increase immunity to a particular disease
time line of vaccine development
early vaccinations=inoculation practised in africa india china, introduced from turkey to england in 18th century
further development=1793 noted immunity of milkmaids of cowpox, took material from human case of cowpox and inserted into arms of child, subsequently inoculated boy with smallpox and found him immune
first rabies vaccine=end of 19th century, developed by isolating, inactivating and injecting infectious agents
mechanisms of immune response
encounter with exogenous substance leads to immune response or no response (immune tolerance)
what is innate and adaptive immunity
innate immunity=fixed responses activated by receptors encoded by genes in host germ line, receptors recognise molecular patterns shared by many foreign substances that arent present in mammalian host
adaptive immunity=responses to unique foreign structures (antigens/immunogens), antigen receptors encode by relatively few gene elements, somatically rearranged to result in assembly of antibodies (antigen binding mc with high specificity for individual immunogens)
innate Immunity=first line of defense, fast response, non specific (same response to all pathogens, includes skin/mucus/phagocytes/inflammation/fever
adaptive Immunity=second line (if innate fails), slower respond, specific to each pathogen, has immunomemmory, includes B cells (antibodies) and T cells
what is an antigen
substance identified as foreign which induces and immune response
what is immunity
ability of an organism to resists infection through presence of WBC and tissue bound circulating antibodies against the antigen
what is acquired immunity
immunity acquired from development of antibodies in response to an antigen (having disease or vaccine)
what is active immunity
ability of bodys cells to respond to antigen and produce antibodies against it
what is immunological memory
capacity of immune system to respond more rapidly and with amplified repspnse to a second contact with a specific antigen
what is passive immunity
immunity produced by injection of antibodies produced from serum of an already immune donor, usually short term immunity
what is attenuation
reduction in strength, intensity, or effect
name the classes of vaccines
live attenuated, inactivated
what are live attenuated vaccines
-contains weakened but alive pathogen
-retain ability to replicate in humans at very low extent
-usually doesnt cause illness, provides continuous antigenic stimulation
-generates immune response ot wild type pathogenic strain
-dependent on sufficient replication to induce protective immunity, can be inhibited by preformed antibodies
-preferable for generally healthy people as single dose is often safe and effective, not for people with weak immune systems or pregnant
examples of live attenuated vaccines, what is it, what does it protect against, developed when, how does it work
oral polio vaccine
-tOPV=trivalent oral poliovirus vaccine=mixture of live attenuated polioviruses of all 3 serotypes to offer lasting protection
-developed in 1950s
-mimics immune response after infection with wild poliovirus but with reduced incidence of spread to CNS
-if infected, OPV protects against polio paralysis by preventing spread of virus to nervous system
-OPV strains also produce local immune response in mucous membranes of intestines which is primary site for poliovirus multiplication
-resultant antibodies inhibit infections of wild type virus
bivalent oral polio vaccine (bOPV)
-replaced tOPV in 2016 for routine immunisation
-contains only attenuated virus of serotypes 1 and 3
-makes better immune response against 1 and 3 than tOPV but no immunity to serotype 2
type 2 OPVs
-stabilising sabin-2 attenuation phenotype by modifying nucleotides in 5’UTR
-attenuate virus by modifying nucleotide sequence of viral capsid by codon deoptimisation
-replace commonly used codons with nonpreffered codons can decrease gene expression resulting in viral attenuation
what are inactivated vaccines
-consists of viral particles/bacteria/other pathogens which have been inactivated by heat
-non replicative and depend on preformed antigen mass to induce and adequate immune response
-not affected by preformed antibodies
-weaker response than live vaccine
-adjuvants and multiple booster injections required for effective immune response against inactivated vaccines
-useful for those who cant take attenuated vaccines like elderly and immunodeficient patients
classes of inactivated vaccines
whole virus=entire virus particle, denatured by heat, reactive chemistries, radiation
split virus=derived from detergent action which breaks virus into non infective subunits
purified subunit vaccines=based on one or more purified components of major antigenic sites of a pathogen
conjugated vaccines=synthesised by coupling polysaccharide to carrier protein, converts T independent antigens into T dependent antigens, facilitates B cells to produce polysaccharide specific antibodies, administered in divided doses as first dose permits immune system to respond and enable amplified response to subsequent doses
toxoid=some pathogens cause disease by secreting exotoxins, weakly immunogenic unless large amount/multiple doses, adjuvants included, in tetanus the principle toxin binds to specific membrane receptors only located in presynaptic motor nerve cells, internalisation and migration of toxin to CNS blocks metabolism of glycine essential for normal function of GABA (gamma amino butyric acid) neurons resulting in excess activity of motor neurons and muscle spasms=characteristics of tetanus
components in a vaccine
active ingredient, tonicity agent, buffer, surfactants, chelating agents, stabilisers, adjuvants
what are stabilisers for
prevent aggregation or denaturation of biopharmaceuticals
whta are adjuvants for
enhance immune response
routes of administration for vaccines
mostly intramuscular but can do intradermal, deep subcutaneous, oral, nasal
important factors in protein formulations also apply to vaccines like…
-need for sterility for parenterals
-stability during storage
-ease of injection
examples of stabilisers
-gelatin=derived from pigs in some live vaccines to protect against temperature induced denaturation, used in uk nasal flu vaccine, MMR vaccine, shingles and chicken pox vaccine
-recombinant human serum albumin (rHSA)
-lyoprotectants and others=sorbitol, sugar, polyols, urea, histidine, medium 199 (solution with amino acids, salts and vitamins)
examples of adjuvants
-aluminium salts, Al(OH)3 or AlPO4=forms depot at injection site resulting in sustained release of antigen, activating cells involved in adaptive immune response, readily taken up by immature dendritic cells, facilitate antigen processing in spleen/lymph nodes leading to development of high affinity clones of antibody producing B cells
requirements for vaccine production
-cost effective
-safe
-rapid production
-high target affinity
-low antigenicity for rest of the host
