Human ascariasis has a global and cosmopolitan distribution, and has been characterized as the most prevalent
neglected tropical disease worldwide. The development of a preventive
vaccine is highly desirable to
complement current
measures required for this
parasitic infection control and to reduce chronic childhood
morbidities. In the present study, we describe the mechanism of
protection elicited by a preventive
vaccine against
ascariasis.
Vaccine efficacy was evaluated after
immunization with three different
Ascaris suum antigen extracts formulated with monophosphoryl
lipid A (MPLA) as an adjuvant
crude extract of
adult worm (ExAD);
crude extract of
adult worm cuticle (CUT); and
crude extract of infective
larvae (L3) (ExL3). Immunogenicity elicited by
immunization was assessed by measuring
antibody responses,
cytokine production, and influx of
tissue inflammatory
cells.
Vaccine efficacy was evaluated by measuring the reductions in the numbers of
larvae in the
lungs of immunized BALB/c
mice that were challenged with A. suum
eggs. Moreover,
lung physiology and functionality were tested by
spirometry to determine
clinical efficacy. Finally, the
role of host antibody mediated
protection was determined by passive transfer of
serum from immunized
mice. Significant reductions in the total number of migrating
larvae were observed in
mice immunized with ExL3 61% (p < 0.001), CUT 59% (p < 0.001), and ExAD 51% (p < 0.01)
antigens in comparison with non-immunized
mice. For the
Ascaris antigen-specific
IgG antibody levels, a significant and progressive increase was observed with each round of
immunization, in
association with a marked increase of
IgG1 and
IgG3 subclasses. Moreover, a significant increase in concentration of
IL-5 and
IL-10 (pre-challenge) in the
blood and
IL-10 in the
lung tissue (post-challenge) was induced by CUT
immunization. Finally, ExL3 and CUT-immunized
mice showed a marked improvement in
lung pathology and
tissue fibrosis as well as reduced pulmonary dysfunction induced by
Ascaris challenge, when compared to non-immunized
mice. Moreover, the passive transfer of specific
IgG antibodies from ExL3, CUT, and ExAD elicited a protective response in naïve
mice, with significant reductions in
parasite burdens in
lungs of 65, 64, and 64%, respectively. Taken together, these studies indicated that
IgG antibodies contribute to protective
immunity.