Practice question

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.