Parasite Vaccines

Question 1

Types of Vaccine

Answer 1

• Live attenuated – generally not practical
• Killed whole organism
• Toxoid – heat or chemically inactivate toxins of bacteria
• Dead (crude) parasite antigens – generally poorly effective
• Defined antigens

Question 2

Rationale for the development of a malaria vaccine

Answer 2

Attenuated sporozoite vaccines can protect rodents/primates/humans against wild-type sporozoite challenge
Individuals living in endemic areas develop clinical immunity

Question 3

Antigens for blocking sporozoite infectivity

Answer 3

PfCSP

PfTRAP

Question 4

PfSPZ Vaccine

Answer 4

Live attenuates sporozoites extracted from the salivary glands of irradiated P. falciparum-infected mosquitoes
High dose required for 100% protection

Question 5

PfSPZ-CVac and PfSPZ-GA1 Vaccines

Answer 5

CVac: attenuated in vivo by concomitant administration of an anti-malarial drug
GA1: attenuated by gene knockout

Question 6

RTS,S Malaria Vaccine

Answer 6

Produced in S cerevisiae, consists of the two proteins RTS and S

Question 7

Phase III RTS,S Trials

Answer 7

3 does 45-51% protection in children
Risk of febrile seizures
Needs 4 doses for efficacy in infants

Question 8

ChAd63/MVA ME-TRAP Malaria Vaccine

Answer 8

Viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) elicits the highest number of antigen-specific T cells in humans
ME-TRAP – multiple epitope plus the Thrombospondin adhesive protein (T cell responses)

Question 9

Alternative targets for malaria vaccines

Answer 9

Parasite-derived glycosylphosphatidylinositol (GPI)

Anti-disease vaccine, vaccine for PAM

Question 10

Targeting the asexual stage

Answer 10

To target the parasite at its most destructive stage
Protection does not necessarily have to block all infection but should reduce blood parasitaemia
= reduce disease severity
Antibodies that block red blood cell invasion
Antibodies that enhance parasite phagocytosis by macrophages; IFNg

Question 11

Pf Reticulocyte-binding protein homologue 5 (Rh5)

Answer 11

Rh5: secreted from apical organelles during invasion
Blocks erythrocyte invasion to high efficiency
Rh5 responses are not naturally high
Detection of Eh5 is correlative of protective clinical outcome
Rh5 binds to human basigin

Question 12

Reasons for the need of a leishmania vaccine

Answer 12

• Treatment is dependent on chemotherapy
• Anti-leishmanial drugs are expensive, toxic, and have intensive regimens (long duration and complicated route of infection – intravenous infusion)
• Drug resistance is common
• It is unlikely that chemotherapy alone will allow disease elimination!

Question 13

Leishmanisation

Answer 13

Injection of viable cultured Leishmania major parasites to produce a controlled lesion in a non-viable area of the skin
Parasites induce benign infections with spontaneous healing after 6-9 months
No longer used - potential for actual infection

Question 14

1st generation vaccine - Leishmaniasis

Answer 14

Whole cell killed promastigote with live BCG as adjuvant

Question 15

Sub-unit Leishmania Vaccines in Clinical Development

Answer 15

Leish F1 recombinant antigens - L.majorL TSA, LeIF, ST-1
Leish F3: IDRI
ChAd63-KH

Question 16

Leishmania vaccines in pre-clinical development

Answer 16

Leish DNA vax
Live attenuated parasites as vaccines
Alternative vaccines

Question 17

Vaccines for canine leishmaniasis

Answer 17

Extremely variable disease
Dogs are main reservoir for zoonotic infection
2 vaccines - Leishmune and Leishtec

Question 18

Vaccination against trypanosomiasis

Answer 18

• No vaccine for prevention or treatment of trypanosomiasis
– Chagas disease – effectively treated with benznidazole and nifurtimox when administered soon after infection
– Most effective methods for prevention: vector control, bednets and blood screening
• Limited research on vaccine development
• Effector mechanisms – strong lytic antibody response, cytotoxic T cells, Th1 cytokines

Question 19

Veterinary Vaccine DICTOL

Answer 19

Live irridiate vaccine for parasitic bronchitis in cattle

Irradiated larvae of the lungworm parasite (Dictyocaulus viviparus), a major cause of lung disease

Question 20

Live Irradiated Vaccines for Worms

Answer 20

• CANINE HOOKWOORM (Ancylostoma caninum)
• SHEEP LUNG WORM (Dictyocaulus filariae)
• FELINE FILARIA (Brugia phangi) – Model for human filaria
• BOVINE SCHISTOSOMIASIS (Schistosoma bovis)

Question 21

Future prospects for hookworm vaccines

Answer 21

Current development targets “hidden antigens” involved in blood feeding in the hookworm gut
Development of controlled human infection with N. americanus

Question 22

Protein vaccine for cestodes

Answer 22

Taenia ovis vaccine
Crude oncosphere (larval forms once ingested) antigens are protective
Dominant antigens of 45-50 kDa were protective
Recombinant antigens gave 94% protection in saponin adjuvant

Question 23

Rationale for Schistosomiasis Vaccine

Answer 23

Evidence that protective immunity can be achieved:

1. the immunization of mice with one dose of irradiated cercariae results in 50% - 70% reduction in adult worm burden which can be increased to over 80% with two or three immunizations
2. in non-permissive animal models (e.g., rats and rhesus macaques), worm elimination proceeds via a coordinated immune response by the host, and
3. human populations following exposure in endemic areas invariably develop some degree of protection naturally

Question 24

Schistosomiasis Sub-Unit Vaccines: rSh28GST

Answer 24

• rSh28GST is safe and immunogenic in phase 1 and phase 2 trials.
• rSh28GST has not progressed to an application for licensure despite completion of a phase 3 efficacy trials.