Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures

Hamzabegovic, Fahreta; Goll, Johannes; Hooper, William F.; Frey, Sharon E.; Gelber, Casey E.; Abate, Getahun

doi:10.1038/s41541-020-0156-y

Cited by 12 publications

(6 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another explanation can be attributed to the variations in experimental procedures for evaluation of the cellular response between the studies. The critical importance of the choice of methods used for the assessment of cell-mediated immunity was recently illustrated in studies of the immune response elicited by Flagellin/F1/V candidate vaccine [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

et al. 2020

View full text Add to dashboard Cite

The recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to those obtained from the actual experiments. Here, humoral and cellular immune responses to two major Yersinia pestis protective antigens, F1 and LcrV, were studied in human donors immunized with the live plague vaccine (LPV) based on the attenuated Y. pestis strain EV line NIIEG. The F1 antigen provided modest specific cellular (mixed T helper 1 (Th1)/Th2 type) and humoral immune responses in vaccinees irrespective of the amount of annual vaccinations and duration of the post-vaccination period. The probing of the F1 overlapping peptide library with the F1-positive sera revealed the presence of seven linear B cell epitopes, which were all also predicted by in silico assay. The immunoinformatics study evaluated their antigenicity, toxicity, and allergenic properties. The epitope TSQDGNNH was mostly recognized by the sera from recently vaccinated donors rather than antibodies from those immunized decades ago, suggesting the usefulness of this peptide for differentiation between recent and long-term vaccinations. The in silico analysis predicted nine linear LcrV-specific B-cell epitopes; however, weak antibody and cellular immune responses prevented their experimental evaluation, indicating that LcrV is a poor marker of successful vaccination. No specific Th17 immune response to either F1 or LcrV was detected, and there were no detectable serum levels of F1-specific immunoglobulin A (IgA) in vaccinees. Overall, the general approach validated in the LPV model could be valuable for the rational design of vaccines against other neglected and novel emerging infections with high pandemic potency.

show abstract

Section: Discussionmentioning

confidence: 99%

Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In a phase 1 study, the Flagellin/F1/V vaccine induced T cells and specific antibody responses and was well tolerated. The results of this trial also suggested higher doses of the vaccine could be tested [193,194]. The ectodomain of matrix protein 2 (M2e) is highly conserved in human epidemic influenza A virus strains, and antibodies against M2e are protective in animal models.…”

Section: Tlr5 Agonist-based Adjuvantsmentioning

confidence: 93%

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Yang

Tseng

et al. 2022

Pharmaceutics

View full text Add to dashboard Cite

Vaccines are powerful tools for controlling microbial infections and preventing epidemic diseases. Efficient inactive, subunit, or viral-like particle vaccines usually rely on a safe and potent adjuvant to boost the immune response to the antigen. After a slow start, over the last decade there has been increased developments on adjuvants for human vaccines. The development of adjuvants has paralleled our increased understanding of the molecular mechanisms for the pattern recognition receptor (PRR)-mediated activation of immune responses. Toll-like receptors (TLRs) are a group of PRRs that recognize microbial pathogens to initiate a host’s response to infection. Activation of TLRs triggers potent and immediate innate immune responses, which leads to subsequent adaptive immune responses. Therefore, these TLRs are ideal targets for the development of effective adjuvants. To date, TLR agonists such as monophosphoryl lipid A (MPL) and CpG-1018 have been formulated in licensed vaccines for their adjuvant activity, and other TLR agonists are being developed for this purpose. The COVID-19 pandemic has also accelerated clinical research of vaccines containing TLR agonist-based adjuvants. In this paper, we reviewed the agonists for TLR activation and the molecular mechanisms associated with the adjuvants’ effects on TLR activation, emphasizing recent advances in the development of TLR agonist-based vaccine adjuvants for infectious diseases.

show abstract

“…Both vaccines, rF1 + rV and rV10, were tested and demonstrated efficacy against pneumonic plague infection in mice, guinea pigs and Cynomolgus macaques [176,177] but not in African green monkeys [125]. Further investigations of enhancing immunogenicity or delivery of these subunit vaccines have been attempted or are ongoing by several groups [178][179][180][181][182][183][184][185]. Y. pestis is a Gramnegative bacterium that expresses multiple potential targets that have been exploited for the development of novel medical countermeasures.…”

Section: Vaccinesmentioning

confidence: 99%

Plague Prevention and Therapy: Perspectives on Current and Future Strategies

et al. 2021

View full text Add to dashboard Cite

Plague, caused by the bacterial pathogen Yersinia pestis, is a vector-borne disease that has caused millions of human deaths over several centuries. Presently, human plague infections continue throughout the world. Transmission from one host to another relies mainly on infected flea bites, which can cause enlarged lymph nodes called buboes, followed by septicemic dissemination of the pathogen. Additionally, droplet inhalation after close contact with infected mammals can result in primary pneumonic plague. Here, we review research advances in the areas of vaccines and therapeutics for plague in context of Y. pestis virulence factors and disease pathogenesis. Plague continues to be both a public health threat and a biodefense concern and we highlight research that is important for infection mitigation and disease treatment.

show abstract

Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures

Cited by 12 publications

References 67 publications

Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Plague Prevention and Therapy: Perspectives on Current and Future Strategies

Contact Info

Product

Resources

About