Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects

Figures & data

Figure 1. Age-standardized disability-adjusted life-year rates from Chagas disease by country (per 100,000 inhabitants).

Data taken from [103].

Figure 2. Partnership for the development of a human therapeutic Chagas disease vaccine.

cGMP: Current good manufacturing practice; GLP: Good laboratory practice; PDP: Product development partnership.

Table 1. Chagas vaccine initiative: proposed target product profile.

Item	Desired target	Minimally acceptable target
Indication	A therapeutic vaccine to prevent the onset of Chagasic cardiomyopathy in patients with indeterminate Chagas disease (as determined by antibody seropositivity using a licensed diagnostic kit) or in determinate patients with early-stage evidence of clinical Chagas disease (as determined by antibody seropositivity, together with cardiac clinical manifestations; i.e., ECG or echocardiographic alterations)	A therapeutic vaccine to delay the onset of Chagasic cardiomyopathy in patients with indeterminate Chagas disease (as determined by antibody seropositivity using a licensed diagnostic kit) or in determinate patients with early-stage evidence of clinical Chagas disease (as determined by antibody seropositivity, together with cardiac clinical manifestations; i.e., ECG or echocardiographic alterations)
Target population	Children (>2 years) and adults	Adults >16 years
Route of administration	Intramuscular injection	Intramuscular injection
Product presentation	Single-dose vials. 1.0 ml volume of delivery	Single-dose vials. 0.5 ml volume of delivery
Dosage schedule	Maximum of two immunizations regardless of age, with the second injection given 1–2 months after the first immunization	Maximum of four immunizations according to a 0, 1–2 months, 4–12 months and 5-year schedule
Warnings and precautions/pregnancy and lactation	Mild-to-moderate local injection site reactions such as erythema, edema and pain, the character, frequency and severity of which is similar to licensed recombinant protein vaccines. Less than 0.001% risk of urticaria and other systemic allergic reactions. Incidence of SAEs no more than licensed comparator vaccines	Moderate local injection site reactions such as erythema, edema and pain. Less than 0.1% risk of urticaria. Temporary cardiac inflammation (carditis) as determined by ECG changes lasting no more than 2–3 weeks following administration of any one dose. Beyond the ECG changes, the incidence of SAEs no more than licensed comparator vaccines
Expected efficacy	80% efficacy at preventing the onset of cardiac complications	80% efficacy of delaying the onset of cardiac complications by ≥10 years
Coadministration	All doses may be coadministered with currently available trypanocidal drugs, as well as heart medicines	Essential heart medicines
Shelf-life	5 years	1 year
Storage	Refrigeration between 2 and 8°C. Cannot be frozen. Can be out of refrigeration (at temperatures up to 25°C) for up to 72 h	Refrigeration between 2 and 8°C. Cannot be frozen. Temperature monitor required
Product registration and WHO prequalification	US FDA, in addition to licensure by COFEPRIS, the Mexican National Regulatory Authority. WHO prequalification of manufacturing facility at Birmex (Mexico City, Mexico)	Licensure by COFEPRIS, the Mexican National Regulatory Authority
Target price	$46, the minimal cost of treating a patient with Chagas	$200, one-fifth of the expected cost of treatment per patient per year

SAE: Serious adverse event.

Wikipedia File: Trypanosomiasis world map. http://en.wikipedia.org/wiki/File:Chagas_disease_world_map_-_DALY_-_WHO2004.svg

 Google Scholar