Parasitic Zoonoses

• Orphan Vaccine Concept: An orphan vaccine is a biologically effective, proven vaccine that targets a neglected or commercially unviable disease condition, resulting in lack of commercial production and distribution.
• Case of To45W Vaccine: The To45W recombinant oncosphere antigen vaccine was developed to protect sheep against Taenia ovis metacestodes (sheep measles). While conferring $\gt 95\%$ protection against cysticercosis, T. ovis causes aesthetic carcass condemnation without acute clinical mortality or human health threat, so pharmaceutical companies ceased commercial production, classifying it as an orphan vaccine.
• Contrast with Commercial Vaccines: Rakshavac-T (Theileria annulata), Dictol (Dictyocaulus viviparus irradiated lungworm vaccine), and Paracox (Eimeria spp.) have established commercial markets.

Correct option: (1) To45W based vaccine

• H11 Recombinant Vaccine Context: Native H11 (a gut microvillar aminopeptidase of Haemonchus contortus) when extracted from the parasite intestine induces $\gt 90\%$ protective immunity in sheep by inducing antibodies that block nutrient digestion.
• Reasons for Recombinant Vaccine Failure:
• Low Antibody Avidity: Antibodies raised against the recombinant protein produced in heterologous expression systems had significantly lower functional binding avidity compared to those targeting native conformation.
• Aberrant Glycosylation: Expression in insect cell/baculovirus systems resulted in non-native core $\alpha1,3$-fucosylation and paucimannosidic glycan structures that masked conformational epitopes.
• Inactive Domain Folding: Crucial catalytic and protective epitopes required authentic tertiary and quaternary folding.
• Inappropriate Expression Systems: Baculovirus and bacterial expression failed to reproduce the precise membrane-anchored tertiary architecture of the native metallopeptidase complex.

Correct option: (3) (A), (B), (C) and (D).

• Comparative Helminth Egg Dimensions in Swine:
• Strongyloides ransomi: Embryonated thin-shelled small eggs measuring approximately $45\text{--}55 \times 25\text{--}35\ \mu\text{m}$ (smallest).
• Ascaris suum: Oval, thick-shelled with a rough, mammillated albuminous coat measuring approximately $50\text{--}70 \times 40\text{--}50\ \mu\text{m}$.
• Macracanthorhynchus hirudinaceus: Thorny-headed worm egg with three protective embryonic layers measuring approximately $90\text{--}100 \times 50\text{--}56\ \mu\text{m}$.
• Fasciolopsis buski: Giant intestinal fluke operculated unembryonated eggs measuring approximately $130\text{--}140 \times 80\text{--}85\ \mu\text{m}$ (largest).
• Ascending Sequence: Sorting from smallest to largest yields (D) < (A) < (C) < (B) (Option 4).

Correct option: (4) (D), (A), (C), (B)

• Severity Classification in Haemonchosis: Because adult female Haemonchus contortus worms are exceedingly prolific (producing $5,000\text{--}10,000$ eggs per female per day), fecal egg counts (FEC) in sheep rise rapidly.
• Standard Diagnostic Tiers (Eggs Per Gram, EPG):
• Mild infection: $\lt 1,000$ EPG
• Moderate infection: $1,000\text{--}5,000$ EPG
• Severe / Heavy clinical haemonchosis: $\gt 8,000$ EPG (often exceeding $10,000\text{--}50,000$ EPG in acute outbreaks associated with severe anaemia, hypoproteinaemia, submandibular oedema, and sudden mortality).
• Clinical Application: Worm burdens exceeding 8,000 EPG correlate directly with severe haematocrit drops ($\lt 15\%$) and require immediate emergency anthelmintic intervention.

Correct option: (3) >8000