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#subunit vaccines

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Vaccine

Subunit vaccines consist of:

Subunit vaccines consist of specific antigenic components derived from pathogen rather than whole organism, representing purified or recombinant fractions capable of eliciting protective immunity. Components include capsular polysaccharides, detoxified toxins, recombinant surface proteins, virus-like particles formed by self assembly. Hepatitis B vaccine contains recombinant HBsAg 22 nm particles produced in Saccharomyces cerevisiae yeast after cloning S gene under alcohol oxidase promoter; human papillomavirus vaccine contains L1 protein VLPs from yeast or insect cells; influenza subunit vaccines contain purified hemagglutinin and neuraminidase after detergent treatment splitting virions; acellular pertussis contains pertussis toxin genetically mutated PT-9K/129G, filamentous hemagglutinin, pertactin and fimbriae 2/3. Advantages include precisely defined composition, inability to cause infection, reduced reactogenicity removing lipopolysaccharide, lower risk in immunocompromised hosts. Limitations include poor innate immunogenicity requiring adjuvants MF59 oil-in-water, AS01 containing QS21 saponin and MPL, aluminum to enhance Dendritic cell recruitment. Many polysaccharides T-independent requiring conjugation to carrier proteins tetanus or CRM197 converting to T-dependent response inducing germinal center memory, crucial for infant vaccines against Haemophilus and pneumococcus.

Ref: Plotkin Subunit specific components; WHO Subunit vaccines; Pulendran Adjuvants.

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Immunological Applications

Subunit vaccines contain:

Whole pathogen vaccines contain complex mixture of antigens including immunodominant protective components but also many irrelevant proteins plus reactogenic factors such as lipid A endotoxin activating TLR4 causing fever, pertussis toxin ADP-ribosylating Gi, increasing reactogenicity and rare adverse events. Subunit vaccine strategy improves safety by purifying protective antigens through biochemical fractionation, recombinant expression, or synthetic peptide synthesis excluding toxic moieties. Hepatitis B vaccine exemplifies recombinant subunit: hepatitis B small surface antigen HBsAg gene cloned into Saccharomyces cerevisiae yeast downstream of alcohol dehydrogenase promoter, protein expressed self-assembles into 22 nanometer virus-like particles composed of 100 monomers with disulfide crosslinks displaying conformational neutralizing a determinant in second hydrophilic loop, particles lack viral DNA completely noninfectious. Acellular pertussis vaccine includes genetically detoxified pertussis toxin PT9K/129G where arginine 9 to lysine and glutamic acid 129 to glycine mutations abolish ADP-ribosyltransferase activity, filamentous hemagglutinin adhesion factor, and pertactin 69 kDa outer membrane protein, eliminating whole cell lipopolysaccharide linked to high fever and protracted crying observed with whole cell DTP.

Ref: NCERT Class XII Biology subunit purified antigen VLP HBsAg; Pulendran Nat Immunol 2011 alum NLRP3 adjuvant acellular pertussis.

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Immunological Applications

Subunit vaccines contain:

Subunit vaccines avoid using whole infectious organism replication-competent incorporating only highly purified antigenic components capable eliciting protective immunity without risk producing disease immunocompromised pregnant elderly. Antigens include recombinant proteins hepatitis B surface antigen HBsAg 226 aa small S self-assembling 22 nm VLPs Saccharomyces cerevisiae Hansenula after methanol induction AOX1 promoter purification density gradient acellular pertussis components pertussis toxoid chemically toxoided formaldehyde hydrogen peroxide inactivation removing ADP-ribosylating activity preserving epitopes filamentous hemagglutinin FHA 220 kDa adhesin pertactin 69 kDa outer membrane fimbriae 2 3 HPV L1 major capsid 360 copies 55 nm VLPs insect Sf9 baculovirus Autographa californica. Manufacturing fermentation fed-batch 10^9 cells/mL downstream chromatography ion exchange anion cation capturing size exclusion polishing affinity monoclonal columns removing host DNA

Ref: Plotkin Vaccines Subunit Concept Hepatitis B HBsAg Yeast; WHO Subunit Vaccine Development Production Guidelines 2022; Janeway Immunology Subunit vs Whole Organism Chapter 12.

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