Typhoid Vaccine

Typhoid vaccines protect against enteric fever caused by Salmonella enterica serovar Typhi by stimulating adaptive humoral immunity to a defined bacterial antigen (the Vi capsular polysaccharide) or, in the case of the oral Ty21a vaccine, to a broader panel of surface antigens of an attenuated live strain. Vaccination does not protect against Salmonella enterica serovars Paratyphi A, B, or C, which can cause clinically indistinguishable paratyphoid fever in the same geographies.

Mechanism of Action

Oral Ty21a (Vivotif)

• Ty21a is a stable mutant of the wild-type Salmonella Typhi Ty2 strain, attenuated by chemical mutagenesis. Loss of the galE gene product (galactose epimerase) and other regulatory genes render the strain incapable of producing complete lipopolysaccharide, eliminating virulence while preserving immunogenicity.
• The enteric coating protects the live organisms from gastric acid; in the small intestine, the bacteria multiply briefly in the gut lumen and Peyer’s patches.
• Induces both systemic IgG to S. Typhi antigens and intestinal secretory IgA — the mucosal antibody response is a distinctive advantage of the oral route and is thought to contribute to protection at the gut entry portal.
• Also generates T-cell responses, including CD8⁺ memory cells.

Injectable Vi polysaccharide (Typhim Vi, Typherix)

• Purified capsular polysaccharide of S. Typhi, a single bacterial antigen.
• T-independent B-cell response — produces serum IgG specific for the Vi antigen but only limited mucosal IgA, no memory B-cell response, and limited boosting on revaccination.
• Onset of protection approximately 2 weeks after a single dose; duration of protection ~3 years.

Injectable Vi-tetanus toxoid conjugate (Typbar TCV and others)

• Vi polysaccharide chemically conjugated to a tetanus toxoid carrier protein, converting the response from T-independent to T-dependent.
• Generates memory B-cell responses, allows immunisation of infants (where Vi polysaccharide alone is poorly immunogenic), and produces longer-lasting protection.
• WHO-prequalified for routine immunisation in typhoid-endemic countries from age 6 months.

Pharmacokinetics

Conventional pharmacokinetic concepts do not apply to vaccines. Relevant immunological parameters:

• Onset of protection: oral Ty21a — protection develops over the 2 weeks after the fourth capsule; injectable Vi polysaccharide — protection at ~14 days post-dose; Vi-conjugate — protection at ~14 days, with stronger and longer responses.
• Duration of protection: oral Ty21a 5–7 years in some studies; injectable Vi polysaccharide ~3 years; Vi-conjugate up to 5 years per current evidence.
• Vaccine efficacy in field trials: 50–80% depending on formulation, host factors, and challenge dose.

• Pre-travel prophylaxis for adults and children travelling to typhoid-endemic regions (South Asia, Sub-Saharan Africa, Southeast Asia, parts of Latin America), particularly for stays >1 month or for shorter visits to areas with poor sanitation, intensive contact with local populations, or visiting friends and relatives (VFR travel).
• Occupational vaccination: laboratory workers handling S. Typhi cultures; sewage and wastewater workers in selected settings.
• Household and close contacts of identified chronic typhoid carriers.
• Outbreak control in endemic settings (typically with Vi polysaccharide or conjugate vaccines).
• Routine paediatric immunisation in endemic countries with WHO-recommended Vi-conjugate vaccines (from 6 months of age).

• Hypersensitivity to typhoid vaccine, any vaccine excipient, or (for conjugate vaccines) the carrier protein.

Specific to oral Ty21a (Vivotif)

• Age <6 years.
• Acute febrile illness (defer until resolved).
• Acute gastrointestinal illness (vomiting, diarrhoea — defer until resolved; bacterial replication and immune response may be impaired).
• Immunosuppression (HIV with significant CD4 depletion, chemotherapy, biologics, high-dose corticosteroids, primary immunodeficiency) — use the inactivated injectable vaccine instead.
• Pregnancy — preference for injectable formulations.
• Concurrent antibiotics active against Salmonella (within 72 hours before or 72 hours after each capsule) — antibiotics may kill the vaccine organism before it stimulates immunity.

Specific to injectable Vi polysaccharide

• Age <2 years (poor immunogenicity).
• Acute febrile illness (defer).

Oral Ty21a (Vivotif) — common: mild nausea, abdominal discomfort, headache, fever, rash, urticaria (rare).

Injectable Vi polysaccharide / conjugate — very common: injection-site pain, erythema, induration.

Injectable — common: fever, headache, myalgia, malaise, nausea.

Uncommon to rare: severe hypersensitivity reactions including anaphylaxis (very rare); local injection-site nodule.

• Antibiotics (particularly those active against Salmonella — quinolones, co-trimoxazole, macrolides, beta-lactams): avoid co-administration with oral Ty21a — antibiotic therapy will inactivate the vaccine. Separate by at least 72 hours.
• Mefloquine (antimalarial): some product information advises a separation of 12–24 hours from oral Ty21a, though evidence is limited.
• Atovaquone/proguanil and chloroquine: no clinically meaningful interaction with oral Ty21a — these can be taken concurrently or with brief separation per product labelling.
• Live virus vaccines: oral Ty21a can be co-administered with other live vaccines (oral polio, yellow fever) without interference.
• Immunosuppressive medication (DMARDs, biologics, high-dose corticosteroids, chemotherapy): reduce or abolish vaccine response; use injectable inactivated formulations and consider timing of immunisation around therapy.
• Cholera vaccine: oral cholera vaccine (Dukoral) can be co-administered with oral Ty21a per product labelling; brief separation may improve immunogenicity.

Oral Ty21a (Vivotif)

• Adults and children ≥6 years: 1 enteric-coated capsule on days 1, 3, 5, and 7 (total 4 capsules). Take approximately 1 hour before a meal with a cool drink (water or milk; the capsule must not be exposed to hot liquid).
• Storage during the course: capsules must remain refrigerated between doses.
• Booster: revaccination every 5 years (some product information suggests 3 years for ongoing exposure or high-risk travellers).

Injectable Vi Polysaccharide (Typhim Vi, Typherix)

• Adults and children ≥2 years: single intramuscular dose of 0.5 mL in the deltoid (adults and older children) or anterolateral thigh (younger children).
• Booster: every 3 years for continued exposure.

Injectable Vi-Conjugate (Typbar TCV)

• Infants and children from 6 months, adolescents, and adults: single intramuscular dose of 0.5 mL.
• Booster: not yet definitively established; current evidence supports protection for at least 5 years.

Renal/Hepatic Impairment

No specific dose adjustment.

Missed Dose (Oral Ty21a)

If a capsule is missed, take it as soon as remembered and continue the alternate-day schedule from that point. If interruption is prolonged, consider restarting the four-capsule course.

Cold Chain

All typhoid vaccines (oral and injectable) require strict 2–8 °C cold-chain maintenance. Even brief temperature excursions, particularly freezing for the injectables and warming for Ty21a, may compromise efficacy. Distribution, storage, and patient handling must protect the cold chain.

Patient Counselling on Travel Hygiene

Even after vaccination, travellers should be counselled on food and water precautions: drink bottled or boiled water, avoid ice, eat only thoroughly cooked food, peel fruit, avoid salads and unpasteurised dairy. Vaccination is an adjunct to, not a substitute for, hygiene.

Paratyphoid Fever

Typhoid vaccines do not protect against S. Paratyphi A, B, or C. In some regions, paratyphoid accounts for a growing fraction of enteric fever cases — vaccination does not eliminate the need for hygiene precautions.

Concurrent Travel Vaccines

Typhoid vaccine can be given with most other travel vaccines (hepatitis A, hepatitis B, yellow fever, meningococcal ACWY, rabies pre-exposure, cholera). For oral Ty21a, note antibiotic timing as above.

Pregnancy and Lactation

• Oral Ty21a (Vivotif): not generally recommended in pregnancy as a precautionary measure (live attenuated). Use injectable inactivated formulations if vaccination is required.
• Injectable Vi polysaccharide and conjugate: can be administered in pregnancy and during breastfeeding when the indication justifies the use (no live components).

Immunocompromised Hosts

Use injectable Vi polysaccharide or Vi-conjugate vaccines; avoid oral Ty21a. Response may be attenuated; consider serology if clinically important.

Effect on Driving

No influence on the ability to drive or use machines.

Strict cold chain at 2–8 °C; do not freeze; protect from light. Maintain refrigeration during patient self-administration of oral Ty21a between capsules. Do not use after the expiry date on the packaging.

Typically 12–24 months from manufacture depending on formulation. Cold-chain integrity is more often the limiting factor than calendar expiry.

Prescription required (Rx). Typically dispensed through travel medicine clinics, hospital pharmacies, and specialised primary care; cold-chain logistics required for distribution. Oral Ty21a is dispensed as a four-capsule blister pack for a single individual.