Typhoid Vaccine

Disease Burden And Rationale

• Enteric fever caused by Salmonella Typhi heavily impacts low-income and middle-income nations.
• Children under 15 years carry highest disease burden.
• Rising extensively drug-resistant strains necessitate effective prevention.
• Immunization reduces transmission, severe complications, and hospitalization.

Vi Capsular Polysaccharide Vaccine

Composition And Immunology

• Comprises 25 µg purified Vi-polysaccharide.
• Functions as T-cell independent antigen.
• Fails to generate immunological memory.

Dosing And Efficacy

• Administered via single 0.5 mL intramuscular or subcutaneous injection.
• Requires minimum age of 2 years due to low immunogenicity in infants.
• Initial efficacy approaches 69% in first year.
• Cumulative efficacy declines to 55% at 3 years.
• Mandates revaccination every 3 years for sustained protection.

Safety Profile

• Mild local pain and swelling frequently observed.
• Safe for immunocompromised individuals including human immunodeficiency virus infected patients.

Typhoid Conjugate Vaccine (TCV)

Mechanism And Advantages

• Links Vi-polysaccharide to carrier proteins like Tetanus Toxoid, Diphtheria Toxoid, or CRM197.
• Transforms T-independent polysaccharide into T-dependent antigen.
• Triggers T-cell dependent humoral responses.
• Generates strong anamnestic response and immune memory.
• Induces herd immunity.

Administration And Efficacy

• Administered as single 0.5 mL intramuscular dose.
• Approved for infants starting at 6 months.
• Demonstrates superior efficacy of 80-85% spanning multiple years.

Formulations Available

• Typbar-TCV utilizes Tetanus Toxoid carrier.
• Typhibev incorporates CRM197 carrier.
• Zyvac TCV employs Tetanus Toxoid carrier.

Live Attenuated Oral Vaccine (Ty21a)

Characteristics

• Utilizes genetically stable mutant S. Typhi Ty21a strain.
• Stimulates intestinal mucosal immunity.
• Administered as enteric-coated capsules.

Limitations

• Inappropriate for young children due to intact swallowing requirement.
• Concurrent antibiotics interfere with immune response.
• Requires revaccination every 3 years.
• Currently unavailable in India.

Current Guidelines

Routine Immunization Recommendations

• TCV preferred over Vi-polysaccharide across all ages.
• Initiated as single dose at 6 months of age.
• Catch-up immunization recommended up to 18 years.
• Booster doses lack sufficient evidence for routine recommendation.

Future Innovations

Bivalent Conjugate Vaccines

• Designed to concurrently target Salmonella Typhi and Salmonella Paratyphi A.
• Integrates Vi-conjugate with O:2 specific polysaccharide conjugate.
• Addresses escalating paratyphoid fever incidence across Asia.
• Preclinical evaluations exhibit robust immunogenicity against both target pathogens.
• Phase 1 clinical trials currently ongoing to evaluate safety and dose-response profiles.