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A single dose sub-unit vaccine protects against pneumonic plague
E D Williamson1, S M Eley, A J Stagg
1DERA (Chemical and Biological Defence Sector), Porton Down, Wiltshire SP4 0JQ, Salisbury, UK. dewilliamson@dera.gov.uk
Insights
A new subunit vaccine for Yersinia pestis (plague) offers superior protection compared to existing whole cell vaccines. This single-dose vaccine fully protected mice against aerosolized plague, demonstrating enhanced efficacy in a pneumonic plague model.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Pneumonic plague, caused by Yersinia pestis, remains a significant public health concern.
- Existing killed whole cell (KWC) vaccines have limitations in protective efficacy.
- Development of effective subunit vaccines is crucial for plague prevention.
Purpose of the Study:
- To compare the protective efficacy of a novel single-dose alhydrogel-adsorbed subunit vaccine against aerosolized Yersinia pestis with an existing licensed KWC vaccine.
- To evaluate the immune response, specifically IgG antibody levels, generated by both vaccine types.
Main Methods:
- An outbred mouse model was used to assess protection against aerosolized virulent Yersinia pestis.
- Mice were vaccinated with either the subunit vaccine or the KWC vaccine.
- Bacterial load in lungs and serum/broncho-alveolar IgG titers against F1 and V antigens were measured post-challenge.
Main Results:
- The subunit vaccine provided full protection against a high dose of aerosolized Yersinia pestis, whereas the KWC vaccine offered only 16% protection.
- Subunit vaccinees cleared bacteria from lungs, while KWC vaccinees showed detectable bacteria.
- Subunit vaccinees exhibited significantly higher F1- and V-specific IgG titers in serum compared to KWC vaccinees.
Conclusions:
- A single dose of the alhydrogel-adsorbed subunit vaccine is highly effective against pneumonic plague in a mouse model.
- The subunit vaccine elicits a superior and more protective immune response than the current KWC vaccine.
- Circulating IgG antibodies to F1 and V antigens are key contributors to the protective efficacy of the subunit vaccine.
Abstract:
In this study, the protection afforded against aerosolised Yersinia pestis by injection of a single dose of an alhydrogel-adsorbed sub-unit vaccine has been compared with that given by an existing killed whole cell vaccine licensed for human use. The sub-unit vaccine, prepared by admixing F1 antigen derived from a Y. pestis cell culture supernatant with recombinant V antigen derived from an E. coli cell lysate, fully protected an outbred strain of mouse against exposure to 10(6) CFU of virulent plague organisms (10(4) mouse lethal doses, MLD). In contrast, the whole cell vaccine provided only 16% protection against the same level of challenge. Furthermore, sub-unit vaccinees were able to clear the bacteria from their lungs post-challenge whereas bacteria were cultured from the lungs of a surviving KWC vaccinee post-challenge. In killed whole cell vaccinees, physiologically significant levels of IgG to F1 only were detectable and the levels of F1-specific IgG in serum and in broncho-alveolar washings were significantly lower (p<0.05) compared with sub-unit vaccinees. In sub-unit vaccinees, an IgG titre to the F1 and V antigens was detected in serum where it was significantly higher (p<0.05) compared with broncho-alveolar washings suggesting that, at the time of challenge, protection is attributable mainly to the combined circulating IgG titre to the F1 and V sub-units. The enhanced protective efficacy of this sub-unit vaccine administered as a single dose compared with an existing vaccine has been demonstrated in an outbred animal model of pneumonic plague.