• Vaccine Ontology ID: VO_0000829
• Type: Subunit vaccine
• Caf1 from Y. pestis biovar Microtus str. 91001 gene engineering:
  • Type: Protein
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0001241
  • Description: Yersinia pestis fraction 1 capsular antigen (F1) is a plasmid (pFra)-encoded, proteinaceous capsule, synthesized in large quantities by the pathogen, and reported to confer antiphagocytic properties on Y. pestis by interfering with complementmediated opsonization. The protein is highly immunogenic and has been indirectly associated with eliciting a protective immune response in humans, as evidenced by the detection of high levels of anti-F1 antibody in F1-immunized volunteers (Andrews et al., 1996).
• Preparation: Partially pure cell-associated (capsular) F1 was extracted and isolated. HIB containing xylose was inoculated with a loop of Y. pestis CO92 Pgm2 Lcr2 from a plate stock and grown. The bacteria were then harvested by centrifugation, and the supernatant was retained for isolation of cell-free F1. The cell pellets were next resuspended and recentrifuged before the supernatants were pooled. Crude cell-associated capsular F1 from the salt extract supernatants was precipitated with ammonium sulfate. Protein that precipitated was collected by centrifugation. Purified, detoxified Y. pestis and E. coli supernatant F1 and cell-extracted F1 were adsorbed to the adjuvant (Andrews et al., 1996).
  
• Virulence:
• Description: Yersinia pestis fraction 1 capsular antigen (F1) is a plasmid (pFra)-encoded, proteinaceous capsule, synthesized in large quantities by the pathogen, and reported to confer antiphagocytic properties on Y. pestis by interfering with complementmediated opsonization. The protein is highly immunogenic and has been indirectly associated with eliciting a protective immune response in humans, as evidenced by the detection of high levels of anti-F1 antibody in F1-immunized volunteers (Andrews et al., 1996).
  

Mouse Response

• Host Strain: female, 8- to.10-week-old outbred (Hsd:ND4) Swiss Webster mice (Harlan Sprague Dawley,Indianapolis, Ind.).
• Vaccination Protocol: Mice were immunized with two hundred microliters of each antigen-adjuvant mixture, containing 10 mg of F1. After 30 days, the animals were boosted with the identical dose at the same inoculation site. Four negative control groups, consisting of 10 mice each, were immunized with the adjuvants only. F1 antibody titers of all animal groups were measured 26 days after the second F1-immunizing dose (Andrews et al., 1996).
• Side Effects: No side effects mentioned.
• Challenge Protocol: The 11 immunized and control animal groups to receive the s.c. challenge were administered 100 50% lethal doses (LD50) of wild-type Y. pestis CO92 (LD50 5 1.9 CFU) 28 days after the F1 booster dose. The second set of 11 animal groups was next exposed in a nose-only exposure chamber to a dynamic aerosol containing the virulent organisms diluted to give an inhaled dose of about 100 LD50 (LD50 5 2.3 3 10^4 CFU). All infected animals were monitored daily for disease symptoms and/or death until 28 days postchallenge. At day 28, surviving animals were bled for anti-F1 titer and euthanized, their spleens were cultured on blood agar base, and viable organisms were counted.
• Efficacy: F1 antigen evoked a high degree of protection in animals challenged s.c. with 100 LD50 of wild-type Y. pestis (70-100% survival). Protection also appeared to be independent of the source of the antigen, whether cell derived or cell free, from either Y. pestis or E. coli, and the adjuvant used. However, results do suggest that F1 combined with Alhydrogel, the only adjuvant approved for human use, elicits good protective immunity at the challenge dose administered. Although not achieving the level of protection seen against s.c. challenge, F1 also protected the majority of immunized mice by aerosol (65-84% survival) (Andrews et al., 1996).

Rat Response

• Host Strain: Rattus norvegicus
• Vaccination Protocol: Rats were vaccinated with F1 antigen in Freund's complete adjuvant. The rats received an injection of 500 ug of F1 followed by booster injections of 200 ug of F1 at 7 and 14 days. These rats were challenged 6 weeks later with 3.5 * 10^3 Y. pestis 195/P(Williams et al., 1979) .
• Persistence: Survival among vaccinated rats was in direct proportion to the titre of F1 antibody titre present at the time of challenge. In vaccinated rats that died, death was directly correlated with the F1 antibody titre at the time of challenge (Williams et al., 1979).
• Side Effects: None noted.
• Efficacy: Inoculation of 1*10^3 to 5*10^5 Y. pestis survived at rates of 6% at titres less than 1:16, 46% at titres of 1:32-1:64, 90% at titres of 1:128-1:256, and 96% at titres of 1:512-1:1024. Rats vaccinated with F1 antigen and rats that had been infected previously were challenged i.n. with 8.9 *10^4 Y. pestis and subsequently demonstrated similar rates of survival that was 0 at titres less than 1:128, 86% at titres of 1:128-1:256, and 100% at titres of 1:512-1:1024 (Williams et al., 1979).
• Description: Exposure to F1, either through vaccination or infection, stimulates the production of antibodies that can be measured quantitatively. At present, the passive haemagglutination (PHA) and haemagglutination-inhibition techniques are most widely employed for this purpose because the procedures are convenient and exhibit great sensitivity and specificity. Although the occurrence of antibody to F1 in man or animals suggests that some degree of protection against reinfection has been acquired, the relationship between the serological titre of F1 antibody and immunity to plague has not been clearly defined. The work reported here investigated the correlation between titre and protection with reference to the PHA procedure for measuring F1 antibody (Williams et al., 1979).