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The Onchocerca volvulus cysteine proteinase inhibitor, Ov-CPI-2, is a target of protective antibody response that increases with age.

Cho-Ngwa F, Liu J, Lustigman S - PLoS Negl Trop Dis (2010)

Bottom Line: Notably, culturing L3 in vitro in the presence of anti-Ov-CPI-2 monospecific human antibodies and naïve neutrophils resulted in almost complete inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.These results add to the knowledge of protective immunity in onchocerciasis and support the possible involvement of anti-Ov-CPI-2 IgG1 and/or IgG3 cytophilic antibodies in the development of protective immunity in the PI and the INF.The results further support the consideration of Ov-CPI-2 as a leading target for an anti-L3 vaccine.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America. chongwa_ub@yahoo.co.uk

ABSTRACT

Background: Despite considerable efforts, a suitable vaccine against Onchocerca volvulus infection has remained elusive. Herein, we report on the use of molecular tools to identify and characterize O. volvulus antigens that are possibly associated with the development of concomitant immunity in onchocerciasis.

Methodology/principal findings: Third-stage larvae (L3) and molting L3 (mL3) O. volvulus stage-specific cDNA libraries were screened with a pool of sera from chronically infected patients who had likely developed such immunity. The 87 immunoreactive clones isolated were grouped into 20 distinct proteins of which 12 had already been cloned and/or characterized before and 4 had been proven to be protective in a small O. volvulus animal model. One of these, onchocystatin (Ov-CPI-2), a previously characterized O. volvulus cysteine proteinase inhibitor was, overall, the most abundant clone recognized by the immune sera in both the L3 and mL3 cDNA libraries. To further characterize its association with protective immunity, we measured the IgG subclass and IgE class specific responses to the antigen in putatively immune (PI) and infected (INF) individuals living in a hyperendemic area in Cameroon. It appeared that both groups had similar IgG3 and IgE responses to the antigen, but the INF had significantly higher IgG1 and IgG4 responses than the PI individuals (p<0.05). In the INF group, the IgG3 levels increased significantly with the age of the infected individuals (r = 0.241; p<0.01). The IgG1 responses in the INF were high regardless of age. Notably, culturing L3 in vitro in the presence of anti-Ov-CPI-2 monospecific human antibodies and naïve neutrophils resulted in almost complete inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.

Conclusions/significance: These results add to the knowledge of protective immunity in onchocerciasis and support the possible involvement of anti-Ov-CPI-2 IgG1 and/or IgG3 cytophilic antibodies in the development of protective immunity in the PI and the INF. The results further support the consideration of Ov-CPI-2 as a leading target for an anti-L3 vaccine.

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The correlation of IgG sub-classes and IgE class responses to rOv-CPI-2 in infected patients with age: Maintenance of high IgG1 (a) and IgE (c) responses regardless of age; (b) Positive correlation between IgG3 levels and age (r = 0.241; P = 0.0013).
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pntd-0000800-g001: The correlation of IgG sub-classes and IgE class responses to rOv-CPI-2 in infected patients with age: Maintenance of high IgG1 (a) and IgE (c) responses regardless of age; (b) Positive correlation between IgG3 levels and age (r = 0.241; P = 0.0013).

Mentions: Since the recombinant Ov-CPI-2 (rOv-CPI-2) protein was identified by immunoscreening with sera from infected individuals 35 years of age or more who are likely to have developed concomitant immunity, it was of interest to investigate the development of the IgG1, IgG3 and IgE antibody responses to the antigen in infected individuals in relation to their age (N = 176 for IgG1 and IgG3 analyses; N = 68 for IgE analysis). Although the IgG1 responses to rOv-CPI-2 antigen were not correlated with age (Fig. 1a), they were relatively elevated in all ages; with an overall 82.4% of IgG1 responders (mean 0.61±0.72). For the IgG1 analysis, there was no significant difference also in the proportion of responders vs. the non-responders in individuals of ≤20 years of age or those >20 years of age. The IgG3 response to the rOv-CPI-2 antigen was, however, positively correlated with age (r = 0.241; p<0.01) (Fig. 1b). For the IgE responses there was no significant correlation with age (Fig. 1c).


The Onchocerca volvulus cysteine proteinase inhibitor, Ov-CPI-2, is a target of protective antibody response that increases with age.

Cho-Ngwa F, Liu J, Lustigman S - PLoS Negl Trop Dis (2010)

The correlation of IgG sub-classes and IgE class responses to rOv-CPI-2 in infected patients with age: Maintenance of high IgG1 (a) and IgE (c) responses regardless of age; (b) Positive correlation between IgG3 levels and age (r = 0.241; P = 0.0013).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2927424&req=5

pntd-0000800-g001: The correlation of IgG sub-classes and IgE class responses to rOv-CPI-2 in infected patients with age: Maintenance of high IgG1 (a) and IgE (c) responses regardless of age; (b) Positive correlation between IgG3 levels and age (r = 0.241; P = 0.0013).
Mentions: Since the recombinant Ov-CPI-2 (rOv-CPI-2) protein was identified by immunoscreening with sera from infected individuals 35 years of age or more who are likely to have developed concomitant immunity, it was of interest to investigate the development of the IgG1, IgG3 and IgE antibody responses to the antigen in infected individuals in relation to their age (N = 176 for IgG1 and IgG3 analyses; N = 68 for IgE analysis). Although the IgG1 responses to rOv-CPI-2 antigen were not correlated with age (Fig. 1a), they were relatively elevated in all ages; with an overall 82.4% of IgG1 responders (mean 0.61±0.72). For the IgG1 analysis, there was no significant difference also in the proportion of responders vs. the non-responders in individuals of ≤20 years of age or those >20 years of age. The IgG3 response to the rOv-CPI-2 antigen was, however, positively correlated with age (r = 0.241; p<0.01) (Fig. 1b). For the IgE responses there was no significant correlation with age (Fig. 1c).

Bottom Line: Notably, culturing L3 in vitro in the presence of anti-Ov-CPI-2 monospecific human antibodies and naïve neutrophils resulted in almost complete inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.These results add to the knowledge of protective immunity in onchocerciasis and support the possible involvement of anti-Ov-CPI-2 IgG1 and/or IgG3 cytophilic antibodies in the development of protective immunity in the PI and the INF.The results further support the consideration of Ov-CPI-2 as a leading target for an anti-L3 vaccine.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America. chongwa_ub@yahoo.co.uk

ABSTRACT

Background: Despite considerable efforts, a suitable vaccine against Onchocerca volvulus infection has remained elusive. Herein, we report on the use of molecular tools to identify and characterize O. volvulus antigens that are possibly associated with the development of concomitant immunity in onchocerciasis.

Methodology/principal findings: Third-stage larvae (L3) and molting L3 (mL3) O. volvulus stage-specific cDNA libraries were screened with a pool of sera from chronically infected patients who had likely developed such immunity. The 87 immunoreactive clones isolated were grouped into 20 distinct proteins of which 12 had already been cloned and/or characterized before and 4 had been proven to be protective in a small O. volvulus animal model. One of these, onchocystatin (Ov-CPI-2), a previously characterized O. volvulus cysteine proteinase inhibitor was, overall, the most abundant clone recognized by the immune sera in both the L3 and mL3 cDNA libraries. To further characterize its association with protective immunity, we measured the IgG subclass and IgE class specific responses to the antigen in putatively immune (PI) and infected (INF) individuals living in a hyperendemic area in Cameroon. It appeared that both groups had similar IgG3 and IgE responses to the antigen, but the INF had significantly higher IgG1 and IgG4 responses than the PI individuals (p<0.05). In the INF group, the IgG3 levels increased significantly with the age of the infected individuals (r = 0.241; p<0.01). The IgG1 responses in the INF were high regardless of age. Notably, culturing L3 in vitro in the presence of anti-Ov-CPI-2 monospecific human antibodies and naïve neutrophils resulted in almost complete inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.

Conclusions/significance: These results add to the knowledge of protective immunity in onchocerciasis and support the possible involvement of anti-Ov-CPI-2 IgG1 and/or IgG3 cytophilic antibodies in the development of protective immunity in the PI and the INF. The results further support the consideration of Ov-CPI-2 as a leading target for an anti-L3 vaccine.

Show MeSH
Related in: MedlinePlus