Abstract
Nematodes are economically important parasites of many livestock species, while others are important human pathogens causing neglected tropical diseases. In both humans and animals, anthelmintic drug administration is the main control strategy, but the emergence of drug-resistant worms, has stimulated the development of alternative control approaches. Among these, vaccination is considered to be a sustainable and cost efficient strategy. Currently, Barbervax® for the ruminant strongylid Haemonchus contortus is the only registered subunit vaccine for a helminth parasite, although a vaccine for the human hookworm Necator americanus is undergoing clinical trials (HOOKVAC consortium). As both these vaccines comprise a relatively small number of proteins there is potential for selection of nematodes with altered sequence or expression of these antigens. Here we compared the genome and transcriptome of H. contortus populations surviving following vaccination with Barbervax® with worms from control animals. Barbervax® antigens are native integral membrane proteins isolated from the brush border of the intestinal cells of the adult parasite and many of them are proteases. Our findings provided no evidence of selective pressure on the specific vaccine antigens in the surviving parasite populations. However, surviving parasites showed increased expression of other proteases and regulators of lysosome trafficking, and displayed up-regulated lipid storage and defecation abilities that may have circumvented the vaccine effect. Despite the minimal evolutionary time monitored within this experiment, genomic data suggest that a hard selective sweep mediated by the vaccine is unlikely. Implications for potential human hookworm vaccines are discussed.
Author Summary Gastrointestinal nematodes are important parasites of humans and livestock species. Their high adaptive potential allows them to develop resistance to the anthelmintic drugs used to control them. Vaccines could also select for resistance ultimately leading to vaccination failure. Here, we provide the first characterization of the genetic and transcriptomic composition of a worm population that survived following vaccination and challenge infection in comparison to a control population. Noticeably, no selection pressure was found on the vaccine targets. Instead, surviving parasites demonstrated increased expression of other genes involved in blood meal digestion that could facilitate survival in response to the vaccine.