TABLE A9-3Ranking of Lead Candidate Necator americanus Vaccine Antigens

Necator americanus antigenTarget of IgE*Measure of efficacy in animal modelEase of manufacture#Known function or structure**Final score‡‡
Reduced adult worm counts (dog)Reduced adult worm counts (hamster)§Prevention of blood loss||Reduced faecal egg counts
ASP2Yes§§23133214/23 (61%)
APR1No22332214/23 (61%)
GST1No23113212/23 (52%)
CP2ND12ND32210/19 (53%)

GST1, glutathione S-transferase 1; IgE, immunoglobulin E; ND, not determined.

*

If individuals naturally infected with hookworm develop IgE to the protein, the antigen is immediately down-selected.

Reflects quintiles (represented by a score out of 5) of the reduced worm burdens of vaccinated dogs challenged with infective larvae compared with the burden of controls.

§

Reflects quintiles (represented by a score out of 5) of the reduced worm burdens of vaccinated hamsters challenged with infective larvae compared with the burden of controls.

||

Each level (from 1 to 3) represents an increment of 0.5 g per ml in the haemoglobin concentration of vaccinated and challenged animals (with 0 representing the concentration in a control group).

Reflects quartiles (represented by a score out of 4) of reduced faecal egg counts in vaccinated animals challenged with infective larvae, compared with controls.

#

A major impediment to the success of efficacious vaccine antigens is the ease and cost-effectiveness with which their production can be scaled up for synthesis according to good manufacturing practices: 0 means it is not feasible; 1 means it is difficult but potentially feasible; 2 means it will give modest yields and a relatively stable protein but substantial process development is required; 3 means it will give high yields of soluble, stable protein with a straightforward scale up for synthesis according to good manufacturing practices.

**

Known protein function and/or structure assists in determining the mechanism of protection and aids process development: 0 means that the function and/or structure are unknown; 1 means that the function or structure is known; 2 means that the function and structure are known.

‡‡

Tally of scores for each category; if a category score was not obtained because the experiment was not carried out, the category is not counted for the final score.

§§

Recognition that naturally infected individuals develop N. americanus ASP2-specific IgE antibodies occurred late in the development process.

From: A9, DEVELOPING VACCINES TO COMBAT HOOKWORM INFECTION AND INTESTINAL SCHISTOSOMIASIS

Cover of The Causes and Impacts of Neglected Tropical and Zoonotic Diseases
The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies.
Institute of Medicine (US) Forum on Microbial Threats.
Washington (DC): National Academies Press (US); 2011.
Copyright © 2011, National Academy of Sciences.

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