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. 2021 Oct;148(12):1497-1508.
doi: 10.1017/S0031182021001141. Epub 2021 Jun 30.

The excretory-secretory antigen HcADRM1 to generate protective immunity against Haemonchus contortus

Mingmin Lu  1 , Xiaowei Tian  1 , Wenjuan Wang  1 , Yang Zhang  1 , Kalibixiati Aimulajiang  1 , Ai-Ling Tian  2 , Charles Li  3 , Ruofeng Yan  1 , Lixin Xu  1 , Xiaokai Song  1 , Xiangrui Li  1
Affiliations

The excretory-secretory antigen HcADRM1 to generate protective immunity against Haemonchus contortus

Mingmin Lu et al. Parasitology. 2021 Oct.

Abstract

The prevention, treatment and control of Haemonchus contortus have been increasingly problematic due to its widespread occurrence and anthelmintic resistance. There are very few descriptions of recombinant antigens being protective for H. contortus, despite the success of various native antigen preparations, including Barbervax. We recently identified an H. contortus excretory–secretory antigen, H. contortus adhesion-regulating molecule 1 (HcADRM1), that served as an immunomodulator to impair host T-cell functions. Given the prophylactic potential of HcADRM1 protein as a vaccine candidate, we hereby assessed the efficacies of HcADRM1 preparations against H. contortus infection. Parasitological and immunological parameters were evaluated throughout all time points of the trials, including fecal egg counts (FEC), abomasal worm burdens, complete blood counts, cytokine production profiles and antibody responses. Active vaccination with recombinant HcADRM1 (rHcADRM1) protein induced protective immunity in inoculated goats, resulting in reductions of 48.9 and 58.6% in cumulative FEC and worm burdens. Simultaneously, passive administration of anti-HcADRM1 antibodies generated encouraging levels of protection with 46.7 and 56.2% reductions in cumulative FEC and worm burdens in challenged goats. In addition, HcADRM1 preparations-immunized goats showed significant differences in mucosal and serum antigen-specific immunoglobulin G (IgG) levels, total mucosal IgA levels, haemoglobin values and circulating interferon-γ, interleukin (IL)-4 and IL-17A production compared to control goats in both trials. The preliminary data of these laboratory trials validated the immunoprophylactic effects of rHcADRM1 protein. It can be pursued as a potential vaccine antigen to develop an effective recombinant subunit vaccine against H. contortus under field conditions.

Keywords: Adhesion-regulating molecule 1; H. contortus; goat; immunization; protective immunity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

None
Graphical abstract
Fig. 1.
Fig. 1.
Expression of rHcADRM1 protein and characterization of anti-rHcADRM1 antibodies. (A) SDS-PAGE analysis of rHcADRM1 protein. Lane 1: rHcADRM1 protein in the soluble cell extracts; lane 2: the resulting rHcADRM1 protein after purification; lane M: protein ladders. (B) Immunoblot analysis for the specificity of purified anti-HcADRM1 IgG. Blots were incubated with goat anti-rHcADRM1 IgG (lane 3) and control goat IgG (lane 4), respectively. Lane M: protein ladders.
Fig. 2.
Fig. 2.
Evaluation of parasitological parameters in trials 1 and 2. (A) The kinetics of FEC of inoculated groups in trial 1. (B) The kinetics of FEC of inoculated groups in trial 2. FEC presented as EPG were denoted as mean ± s.d. (n = 5 for each group). (C) Cumulative FEC in inoculated groups in trial 1. (D) Cumulative FEC in inoculated groups in trial 2. Cumulative FEC were calculated using the linear trapezoidal method by assessing the area under the curve, and the data were shown as minimum to maximum (group size n = 5). Non-parametric Mann–Whitney tests were used to determine P values. (E) Enumeration of abomasal male, female and total worm burdens in trial 1. (F) Enumeration of abomasal male, female and total worm burdens in trial 2. Worm burdens in each group were presented as minimum to maximum (group size n = 5). The two groups significantly differed at P < 0.05. ns, not significant.
Fig. 3.
Fig. 3.
Mucosal antigen-specific IgG and total IgA production. (A) Mucosal anti-rHcADRM1 IgG levels in trial 1. (B) Mucosal anti-rHcADRM1 IgG levels in trial 2. (C) Total mucosal IgA productions in trial 1. (D) Total mucosal IgA productions in trial 2. The levels of mucosal antibody productions were denoted as minimum to maximum (n = 5 for each group). Statistical analysis of mucosal antibody responses was carried out using non-parametric Kruskal–Wallis tests. The asterisks indicate significant differences between groups (*P < 0.05).
Fig. 4.
Fig. 4.
Circulating antibody responses in the trials. Serum samples were collected throughout all time points, and the kinetics of anti-rHcADRM1 IgG and total IgG productions in the circulation was determined in both trials 1 (A and C) and 2 (B and D). Serum antibody levels in each group (group size n = 5) were denoted as mean ± s.d. The asterisks indicate significant differences between groups B and C or groups E and F (*P < 0.05, **P < 0.01 and ****P < 0.0001).
Fig. 5.
Fig. 5.
Evaluation of haematologic abnormalities in both trials. (A) Kinetics of peripheral blood eosinophils in trial 1. (B) Kinetics of peripheral blood eosinophils in trial 2. (C) Kinetics of haemoglobin in peripheral blood in trial 1. (D) Kinetics of haemoglobin in peripheral blood in trial 2. (E) Kinetics of haematocrit in peripheral blood in trial 1. (F) Kinetics of haematocrit in peripheral blood in trial 2. The levels of eosinophils, haemoglobin and haematocrit in each group were denoted as mean ± s.d. (group size n = 5). Data points followed by asterisks indicate significant differences compared with the challenged controls (group C or F) (*P < 0.05 and **P < 0.01).
Fig. 6.
Fig. 6.
Variation in circulating cytokine levels in both trials. The kinetics of serum IL-4 (A and B), IL-17A (C and D) and IFN-γ (E and F) levels in each group were assessed throughout all time points in trials 1 and 2. Circulating IL-4, IL-17A and IFN-γ expression levels in each group were presented as mean ± s.d. (group size n = 5). The data points denoted by different letters indicate significant differences between groups (P < 0.05).
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References

    1. Bakker N, Vervelde L, Kanobana K, Knox D, Cornelissen A, De Vries E and Yatsuda A (2004) Vaccination against the nematode Haemonchus contortus with a thiol-binding fraction from the excretory/secretory products (ES). Vaccine 22, 618–628. - PubMed
    1. Balic A, Bowles V and Meeusen ENT (2002) Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite Immunology 24, 39–46. - PubMed
    1. Balic A, Cunningham C and Meeusen ENT (2006) Eosinophil interactions with Haemonchus contortus larvae in the ovine gastrointestinal tract. Parasite Immunology 28, 107–115. - PubMed
    1. Bassetto C, Silva B, Newlands G, Smith W and Amarante AD (2011) Protection of calves against Haemonchus placei and Haemonchus contortus after immunization with gut membrane proteins from H. contortus. Parasite Immunology 33, 377–381. - PubMed
    1. Besier R, Kahn L, Sargison N and Van Wyk J (2016a) Diagnosis, treatment and management of Haemonchus contortus in small ruminants. Advances in Parasitology 93, 181–238. - PubMed

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