L6 - Hookworm (First human helminth vaccine?)

Question 1

Which stage is invasive? ?

Answer 1

L3

Question 2

Symptoms

Answer 2

Ground itch

Pulmonary migration

Peripheral eosinophilia

Protein loss – weight loss, growth stunting, cognitive function

Anaemia

Question 3

L3 two most abundant secreted molecules are proteases:

Answer 3

Ancylostoma secreted proteases – ASPs – ASP-1, ASP-2

Na-ASP-1 Na-ASP2

Question 4

Epidemiology

Answer 4

Prevalence increases with age

Overdispersion

Question 5

Th response and relevant immunoglobulin

Answer 5

Generally fits in with Th2 type responses

Elevated levels of parasite specific IgE

Question 6

Vaccines… a possibility

Answer 6

Irradiated L3 larvae induce good immunity to re-infection (antibody mediated)

antibodies are directed against antigens secreted during L3 larval invasion
(ASP-1 and ASP-2)

Question 7

Phase I trial in Americanihas, Minas Gerais, Brazil

Answer 7

10ug vaccination

Within 1-2 hours, 3 experienced acute, generalised urticaria on back, head and upper torso

Given anti-histamines, two resolved, one required treatment for 2 days

found to have significant levels of anti-NaASP-2 IgE

Question 8

Alternative approaches?

Answer 8

1) Inhibit Na-APR -1 (prevents Hb digestion)
2) Lipid Core peptide delivery
3) Fuse to other parasite antigen
4) Recombinant Na-GST-1 is produced in E. coli
5) Na-APR -1 recombinant protein is produced in tobacco plants.

Question 9

Centre de Researches Médicales de Lambaréné, Gabon

Answer 9

Endemic for hookworm

All participants with helminths given anthelmintic before vaccination

Before vaccination of both GST and APR

Question 10

Recent study (Adegnika AA et al, Lancet, September 11, 2020)

Answer 10

Co-administration of Na-GST-1 and Na-APR -1 (plus adjuvant). Three doses of 30ug or 100ug of each i.m. Day 0, Day 28 , Day180

Hookworm specific IgG responses

Good strong AB class with IgG response = good to believe generating level of right Ab and not IgE that could protect against infection

Question 11

Taking vaccination studies forward

Answer 11

Produce food quality clean Necator L3 to carry out control vaccination studies

Monitor adverse events after administration

3 dose = much more reproducibility in number of larvae and infection that establish without increasing any adverse events