February 16, 2018

Reverse Vaccinology: A New Approach to Controlling Cat Fleas

An alternative method of vaccine development shows promise for controlling flea infestations in domestic cats.
By JoAnna Pendergrass, DVM
Ctenocephalides felis, the domestic cat flea, is found worldwide. It causes such clinical signs as allergic reactions and general discomfort and transmits such pathogens as Yersinia pestis that impact human health. Cat flea control is challenging and often requires a multimodal approach with insecticides that disrupt growth and development. C. felis, though, is reportedly becoming resistant to these compounds.

Vaccines are an environmentally friendly alternative to insecticides. Rather than prevent infestations, vaccines reduce infestations by negatively affecting an ectoparasite’s biological activity after it feeds on an immunized animal. To date, vaccine development against C. felis has been limited due to the overall difficulty of identifying protective antigens against ectoparasites and a lack of genetic information on Ctenocephalides spp fleas.

RELATED:
Reverse vaccinology, which uses omics technologies (transcriptomics, proteomics) to screen a pathogen’s genome and identify potential protective antigens, has been used with success in developing antibacterial and anti-tick vaccines. The authors of a recent Parasites & Vectors publication reported the use of reverse vaccinology to identify protective antigens for controlling cat flea infestations.

Identifying the Antigens
The investigators extracted RNA and protein from unfed male and female domestic cat fleas. They then used transcriptomics (RNA transcript analysis) and proteomics (large-scale protein analysis) to select genes encoding 6 candidate protective antigens with functions potentially relevant to cat flea biology:
  • F1: energy metabolism regulation
  • F2: cellular volume and energy regulation
  • F3: proteolytic cascade regulation
  • F4: regulation of insect development and reproduction
  • F5: general development
  • F6: development and immune response

Vaccinating the Cats
The antigens’ genes were cloned using reverse transcriptase PCR to produce recombinant proteins that were then formulated into vaccines. Healthy domestic cats received subcutaneous injections of either the vaccines or adjuvant (control) on study days 0 and 14, then were infested with adult unfed fleas on study day 28.

The investigators collected blood from all cats before immunization and before and after infestation to analyze the IgG response. They also determined vaccine efficacy by analyzing 6 factors of cat flea development:
  • Flea fertility
  • Flea viability
  • Flea mortality
  • Flea fecundity
  • Oviposition
  • Egg hatchability

Results
IgG
The IgG response remained higher in immunized cats than in control cats throughout the study. Further analysis demonstrated that the immunized cats’ sera “recognized the recombinant proteins, showing that the IgG antibody response in vaccinated cats was directed against these protective antigens,” the authors wrote.

Vaccine Efficacy
Overall vaccine efficacy ranged from 32% to 46%. Compared with controls, vaccination with each protective antigen reduced egg hatchability and flea fertility, but had no effect on flea mortality or fecundity. A few of the antigens reduced oviposition and flea viability.

In control and immunized cats at infestation, the investigators observed reduced egg hatchability and fertility with increasing antibody levels. This negative association indicated an important relationship between vaccination and cat flea reproductive capacity. The vaccines’ effect on hatchability and fertility correlate with the metabolic and developmental functions of the protective antigens, the authors noted.

Bringing It Together
The study’s findings support the use of vaccines to control cat flea infestations, the authors concluded. Reverse vaccinology can help improve the identification of protective antigens that negatively affect cat flea reproduction and development. These antigens, the authors suggested, could be used singly or in combination in vaccines to achieve effective cat flea control.

 
Dr. Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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