Efficacy of a PP2A vaccine for Angiostrongylus costaricensis against rat lungworm disease caused by Angiostrongylus cantonensis in wild-caught rats (Rattus rattus) in Hawaii

Abstract

The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes an emerging infectious disease known as neuroangiostrongyliasis or rat lungworm disease. This study evaluates the efficacy of a vaccine developed for a related species, Angiostrongylus costaricensis, to A. cantonensis in the definitive rat host. Wild-caught rats (Rattus rattus) (n = 28) were mated in captivity to produce uninfected F1 progeny. A total of 43 F1 rats were involved in this trial; 20 non-vaccinated, 21 vaccinated, and two unvaccinated, uninfected. F1 offspring in the vaccinated group were intranasally vaccinated with two doses of PP2 A vaccine, a serine/threonine phosphatase 2 A at a dose of 4 μg vaccine and 4 μg adjuvant/25 g body weight at >3 mos. of age. Unvaccinated rats similarly received 4 μg adjuvant/25 g body weight. Rats were gavaged with 50 L3 stage larvae at ~four weeks post-treatment. Necropsies were conducted at 47-50 days post-live challenge and spleen weight, spleen length, lung and heart weights, and the numbers of worms in heart and lungs were recorded. An average of 23.17 adult worms were found among all F1 rats. We found no significant differences between vaccinated and unvaccinated rats in rat body weight (p = 0.883), spleen weight (p = 0.963), spleen length (p = 0.830), lung weight (p = 0.830), heart weight (p = 0.849), and number of worms in heart and lungs (p = 0.621). A TaqMan™ Custom Array (Applied Biosystems) cytokine assay was used to evaluate gene expression of 12 different cytokines in spleen tissue from 23 rats and no significant differences in cytokine (C_T) levels were observed between vaccinated and unvaccinated rats (p values range 0.154-0.988). Thus, the A. costaricensis PP2A vaccine, under these conditions, did not provide adequate protective immunity to guard against infection by A. cantonensis in wild rats.

Keywords: Angiostrongyliasis; Angiostrongylus cantonensis; Angiostrongylus costaricensis; PP2A vaccine; Rat lungworm.