#immunization

Vaccine

The cold chain in vaccination refers to:

Cold chain in vaccination encompasses system ensuring vaccines maintained within manufacturer recommended temperature range during storage and transport from production facility through national, regional, district stores to health centers and outreach vaccination sessions preserving potency until moment administration. Term refers to low temperature preservation, not manufacturing or injection method. Typical vaccines requiring 2 to 8C refrigeration include DTP, hepatitis B, pentavalent, IPV, BCG; some lyophilized vaccines stable at ambient during transport but reconstituted require immediate

Ref: WHO Cold chain storage transport low temperature 2-8C; WHO PQS devices catalog; CDC storage.

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Vaccine

A limitation of polysaccharide vaccines is that they:

Polysaccharide vaccines face intrinsic limitation that they induce serotype specific immunity due to structural diversity of capsular polysaccharides among bacterial strains. For instance Streptococcus pneumoniae possesses greater than 90 serotypes each with distinct repeating unit composition differences in sugar sequence, glycosidic linkage alpha 1-3 vs beta 1-4, side chains and O-acetylation patterns dictating distinct antigenic epitopes. Antib Antibodies raised against polysaccharide of serotype 14 recognizing beta-D-galactose 1-4 linkage do not cross react with serotype 19F containing glu

Ref: Geno Immun Rev Polysaccharide serotype specific; Plotkin Pneumococcal limitation serotype; WHO.

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Vaccine

Diphtheria and tetanus vaccines are examples of:

Diphtheria and tetanus vaccines belong to toxoid class defined by formalin inactivated exotoxins maintaining immunogenicity while lacking toxicity. Diphtheria vaccine contains diphtheria toxoid derived from Corynebacterium diphtheriae Park-Williams 8 strain carrying corynebacteriophage tox gene encoding ADP-ribosyltransferase secreted into culture medium purified then detoxified. Tetanus vaccine uses tetanus toxoid from Clostridium tetani Harvard strain fermenter grown anaerobically producing tetanospasmin. Both toxoids formulated with aluminum phosphate or hydroxide adjuvant as DT, Td, DTP co

Ref: WHO Tetanus Diphtheria toxoid vaccines; Plotkin Toxoid category; Rappuoli.

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Vaccine

Which chemical is commonly used to inactivate toxins in toxoid vaccines?

Toxoid vaccines prevent disease caused by potent bacterial exotoxins rather than bacterial invasion itself. Diphtheria toxin 58 kDa AB toxin ADP-ribosylates elongation factor eEF2 halting protein synthesis causing myocardial necrosis, neuritis; tetanus toxin tetanospasmin 150 kDa metalloprotease cleaves VAMP synaptobrevin preventing inhibitory neurotransmitter release causing spastic paralysis. Native toxins lethal at nanogram per kg doses far too dangerous for direct use. Formaldehyde formalin approximately 37 percent formaldehyde aqueous solution discovered by Gaston Ramon 1923 to detoxify t

Ref: Rappuoli Nat Rev Microbiol Toxoid formalin; Glenny 1920s Toxoid; WHO Toxoid production formalin.

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Vaccine

Inactivated vaccines usually require:

Inactivated vaccines usually require multiple doses and periodic boosters to achieve and sustain protective immunity because non replicating antigen provides transient immune stimulation. Initial dose primes naive B cells in draining lymph nodes producing low affinity IgM and modest IgG, small memory pool, titer often below correlate of protection threshold. Second dose administered 4-8 weeks later triggers anamnestic response with larger germinal center reaction, extensive somatic hypermutation in dark zone mediated by activation induced cytidine deaminase, affinity maturation, isotype class

Ref: Plotkin Why inactivated needs multiple doses; WHO Immunization schedule; Amanna Duration.

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Vaccine

Inactivated vaccines differ from live vaccines because they:

Inactivated vaccines fundamentally differ from live attenuated vaccines because they cannot replicate within host tissues. Inactivation achieved by chemical agents formaldehyde crosslinking proteins, beta-propiolactone alkylating nucleic acids, heat denaturation destroying polymerase enzymes, while preserving epitopes for antibody recognition. Because genome destroyed, no progeny virions produced, infection cycle aborted, inability to cause disease even if host immunocompromised. Immunologically absence of cytosolic replication reduces engagement of RIG-I, MDA5 cytosolic sensors sensing replic

Ref: Baxter J Clin Virol 2007 Inactivated cannot replicate; Plotkin Inactivated vs Live difference; CDC.

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Vaccine

Which vaccine is administered orally?

Oral polio vaccine OPV is classical example administered via oral route as drops rather than injection. Formulated by Albert Sabin in 1957 containing live attenuated poliovirus types 1,2,3 propagated in primary monkey kidney cells, stabilized with MgCl2, sucrose, buffered. Oral delivery mimics natural fecal oral transmission of wild poliovirus. Attenuated virus replicates in M cells of Peyer's patches, gut associated lymphoid tissue generating strong intestinal secretory IgA preventing colonization and transmission, plus systemic IgG and intestinal CD4 T cells. Advantages include easy administ

Ref: WHO OPV oral vaccine; Sabin J Exp Med 1957; Plotkin Polio oral route.

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Vaccine

Live attenuated vaccines are contraindicated in:

Live attenuated vaccines contraindicated in immunocompromised individuals because control of limited replication depends on intact innate and adaptive immune compartments. Immunocompromise includes congenital severe combined immunodeficiency affecting T cells, chronic granulomatous disease phagocyte defect, HIV with CD4 count below 200 cells per microliter in adults or below 15 percent in children, chemotherapy causing neutropenia, high dose systemic corticosteroids more than 2 mg per kg prednisone for 2 weeks, biologic agents anti TNF monoclonal antibodies, organ transplant recipients receivi

Ref: CDC Contraindications immunocompromised live; Plotkin Immunocompromised host; Red Book AAP.

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Vaccine

A major advantage of live attenuated vaccines is:

Major advantage of live attenuated vaccines lies in induction of strong, durable, broad immunity closely mimicking natural infection without causing disease in immunocompetent hosts. Limited replication provides continuous antigen synthesis over days to weeks prolonging immune exposure far beyond bolus injection of killed antigen, sustaining germinal center reactions, affinity maturation and generation of long lived plasma cells producing high affinity IgG persisting decades and memory B cells. Activation of cytosolic innate sensors RIG-I, MDA5, STING by replicating nucleic acids induces robus

Ref: Amanna Nature Medicine 2007 Live vaccine long immunity; Plotkin Advantage robust; Pulendran.

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Vaccine

Live attenuated vaccines are weakened by:

Live attenuated vaccines are weakened by serial passaging in non natural host cell cultures, tissues or under suboptimal temperature forcing accumulation of adaptive mutations and deletion of virulence genes. Method pioneered by Louis Pasteur for anthrax and rabies via passage in animals. For viral vaccines, poliovirus Sabin strains passaged in monkey kidney and mouse spinal cord selecting neurovirulence attenuating mutations in 5'UTR internal ribosome entry site reducing replication in neurons while retaining replication in gut. Measles Edmonston strain passaged in primary human kidney cells,

Ref: Pasteur attenuation principle; Plotkin live vaccine passage; WHO Live attenuated methods.

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Vaccine

Which of the following is NOT a whole-microbe vaccine?

Whole microbe vaccines contain complete intact microorganism either living attenuated with reduced virulence but replicating or killed inactivated retaining structural integrity but replication abolished. Examples live BCG, measles MMR, oral polio, live influenza cold adapted; killed whole cell pertussis, inactivated polio IPV, rabies, influenza whole virion. Subunit vaccines diverge by containing only specific antigenic components rather than entire organism, thereby not considered whole microbe. They include purified capsular polysaccharides, polysaccharide-protein conjugates, acellular pert

Ref: Plotkin Vaccines Chapter Classification whole microbe vs subunit; WHO Vaccine types.

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Vaccine

A vaccine is best defined as:

A vaccine is best defined as immuno-biological product containing all or part of microorganism or its products, synthetic or recombinant antigens, mRNA or viral vector engineered to express antigen, formulated to induce active acquired protective immunity against specific infectious disease or tumor without causing disease itself. It comprises immunogenic principle plus diluents, stabilizers such as sucrose, surfactants, buffers maintaining pH, preservatives like 2-phenoxyethanol preventing bacterial contamination in multidose vials, and sometimes adjuvants aluminum salts, MF59, AS01 enhancing

Ref: WHO Vaccine definition; Plotkin Vaccines 7th ed Ch 1 immunobiological; CDC NIP.

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