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#medical microbiology

14 public questions tagged with this topic.

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 switching to IgG1 and IgG3 high neutralizing activity, expansion of long lived plasma cells homing bone marrow. Third dose further raises affinity. However antibody wanes over months to years because antigen depot cleared quickly unlike replicating live vaccine persisting weeks. Therefore boosters at 12-18 months and school entry maintain immunity. Examples hepatitis B series three doses at 0,1,6 months achieving seroprotection 95 percent, IPV three doses plus booster, DTP five doses. Reliance on multiple doses impacts compliance, coverage, programmatic cost, requiring tracking immunization records, reminder systems. Adjuvants reduce number but still need repeat exposures; oral live vaccines require single dose.

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

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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 administration by volunteers without training, low cost, non sterile technique, secondary spread to contacts via fecal shedding increasing community immunity, cold chain still required but thermostable formulations being developed. OPV contributed to near eradication reducing polio cases 99 percent since 1988. However rare reversion of attenuating mutations in 5'UTR and VP1 capsid leads to vaccine derived poliovirus VDPV causing paralysis and circulating cVDPV outbreaks, prompting switch to inactivated IPV in many countries. Other oral vaccines include rotavirus pentavalent, cholera WC-rBS, typhoid Ty21a illustrating mucosal immunity advantages.

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

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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 robust type I interferon, IL-12, potent CD8 cytotoxic T cell differentiation producing IFN gamma and perforin granzyme killing infected cells, important for viral clearance. Mucosal live vaccines like OPV and rotavirus elicit secretory IgA at portal entry preventing colonization transmission. Single dose often sufficient, sometimes lifelong, reducing programmatic complexity, compliance issues and costs compared to multiple booster schedules required for inactivated vaccines. Examples measles vaccine protection documented more than 20 years, yellow fever 30 years. However safety concern in immunocompromised due to potential progressive infection requires screening contraindications, outweighing advantage in vulnerable populations.

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

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