Vaccine comprising drug and parasite administration
Inventors
Good, Michael • STANISIC, Danielle • LOW, Leanne
Assignees
Publication Number
US-11406694-B2
Publication Date
2022-08-09
Expiration Date
2036-10-24
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Abstract
Apicomplexan parasites or red blood cells infected with apicomplexan parasites are administered to an animal in combination with a delayed death agent that initially allows parasite replication but subsequently kills the apicomplexan parasites. This allows the elicitation of an immune response by the animal while preventing the parasites producing a serious infection of the animal. The apicomplexan parasites may be malaria or babesia parasites. The delayed death agent may be a tetracycline class antibiotic, a macrolide antibiotic or a lincosamide antibiotic.
Core Innovation
The invention provides an immunogenic composition and methods for co-administering blood-stage apicomplexan parasites or red blood cells infected with such parasites alongside a delayed death agent. This combination allows the parasites to replicate initially but subsequently kills them before a serious infection develops, thereby eliciting a protective immune response in the animal. The delayed death agent targets the apicoplast organelle within the parasites, allowing limited replication cycles before parasite death.
The problem addressed concerns the difficulty in developing effective vaccines against blood-stage malaria and other apicomplexan parasites. Prior approaches using whole parasite vaccines required extremely large parasite doses and adjuvants unsuitable for humans, while subunit vaccines have not progressed successfully beyond certain trial stages. Additionally, administration of live parasites posed safety risks if drug treatment was delayed or missed and did not reliably induce a protective immune response without adverse infection.
The invention overcomes these issues by using a low dose of live blood-stage apicomplexan parasites combined with a delayed death antibiotic agent, such as doxycycline, a tetracycline, macrolide, or lincosamide antibiotic. This approach achieves immunization without the need for adjuvants, safely limits parasite replication to induce a robust T cell immune response, and prevents symptomatic infection. It applies broadly to apicomplexan parasites including malaria parasites of various species and Babesia parasites.
Claims Coverage
The patent contains multiple independent claims directed to methods of eliciting protective immune responses and immunizing animals against apicomplexan parasite infections by co-administering blood-stage parasites or infected red blood cells with a delayed death agent.
Method of eliciting protective immune response by co-administration
A method involving identifying an animal and co-administering within 48 hours by injection blood-stage apicomplexan parasites or infected red blood cells and a delayed death agent selected from tetracycline or macrolide antibiotics to produce a controlled avirulent infection eliciting a protective immune response.
Method of immunizing against apicomplexan parasite infection by co-administration
A method involving identifying an animal and co-administering within 48 hours by injection blood-stage apicomplexan parasites or infected red blood cells and a delayed death agent selected from tetracycline or macrolide antibiotics to produce a controlled avirulent infection eliciting an immune response that immunizes the animal.
Exclusion of adjuvant administration
Methods that do not include administering an adjuvant when performing immunization or eliciting an immune response.
Use of slow, controlled, or delayed release formulations of the delayed death agent
Methods where the delayed death agent is formulated in a slow, controlled, or delayed release form to regulate the timing of parasite replication inhibition.
Temporal window for administration to allow limited parasite replication
Administration of parasites and delayed death agent within a temporal window whereby the delayed death agent allows no more than one to five parasite replication cycles before killing the parasites.
Multiple dosing regimens
After initial administration, one or multiple further doses of parasites and/or delayed death agent may be administered to the animal to maintain or bolster the immune response.
Specific methods for bovines against Babesia infections
Methods specifically adapted for bovine animals involving co-administration within 48 hours of blood-stage Babesia parasites or infected red blood cells and a delayed death agent selected from tetracycline or macrolide antibiotics, optionally with slow, controlled, or delayed release formulations and multiple dosing.
The claims collectively cover methods of safely eliciting protective immune responses and immunizing various animals, including humans, bovines, and canines, against apicomplexan parasites by co-administering blood-stage parasites or parasitized red blood cells with delayed death agents, excluding adjuvants, employing specific dosing windows, and using controlled release formulations to manage parasite replication and immune activation.
Stated Advantages
Allows effective immunization against blood-stage apicomplexan parasites while preventing serious infection by permitting limited parasite replication before killing.
Obviates the need for adjuvants, enabling safer and more practical vaccine formulations.
Enables use of low-dose live parasites, overcoming logistical challenges of large-scale vaccine production.
Induces strong cellular (T cell) immune responses with little to no reliance on antibody production.
Provides protection against heterologous strains and species of apicomplexan parasites.
Facilitates controlled avirulent infections useful for safe immunization and for generating animals for vaccine testing.
Reduces costs and risks associated with vaccine efficacy studies by enabling controlled infections in non-endemic regions with smaller sample sizes.
Documented Applications
Vaccination of humans, bovines, and canines against apicomplexan parasite infections such as malaria and babesiosis.
Production of immunogenic compositions comprising blood-stage apicomplexan parasites and delayed death agents for immunization and treatment.
Methods for eliciting immune responses and immunizing animals against blood-stage infections of malaria parasites like Plasmodium falciparum, vivax, chabaudi, yoelii, and Babesia parasites.
Generation of controlled avirulent parasite infections in animals for vaccine efficacy testing.
Use of slow release or controlled release formulations of delayed death agents to regulate parasite replication during immunization.
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