Typhoid fever and Paratyphoid A fever are infectious diseases caused by bacteria known as Salmonella Typhi and Salmonella Paratyphi A. These infections may be acquired by consumption of food or water contaminated with these bacteria. These infections are characterized by fever, chills, headache, decreased appetite, abdominal pain, fatigue, and cough. Some patients may have serious complications like prolonged high fever lasting several weeks, or may have bleeding from digestive tract.

Typhoid fever and Paratyphoid A fever can be treated with antibiotics. However, in recent years, these bacteria have developed resistance to most of the antibiotics, which makes the treatment complicated.

Typhoid fever can be prevented by use of typhoid vaccine. Several typhoid vaccines are available and are safe and efficacious. These typhoid vaccines are indicated for use in 6 months to 65 years age group population. However, there is no vaccine which can prevent Paratyphoid A fever.

Serum institute of Indian (SII) has developed a vaccine, SII Typhoid Conjugate Vaccine (Bivalent) [SII-TCV(B)], which may provide protection against both these infections. This vaccine contains some parts of both Typhoid and Paratyphoid A bacteria, which may help to develop an immune response and protect against the diseases. The SII-TCV(B) has been proven to be safe and generate immune response to vaccine components in animal studies as well as in Phase 1 study conducted in India. This phase 1 study was conducted in 60 healthy adults in age group of 18-45 years in comparison to an already licensed typhoid vaccine known as TYPBAR-TCV®, manufactured by Bharat Biotech.

A total of 651 healthy infants aged 9 months to 12 months will take part in a Phase 2/3 study planned to assess the safety and immune response of SII-TCV(B) in comparison to TYPBAR-TCV® in Kenya in the age group of 9 months to 12 Months. The SII Typhoid Conjugate Vaccine (Bivalent) is the ‘study vaccine’ and Typbar-TCV® is the ‘licensed vaccine.’ Enrolled children will receive either a study vaccine or a licensed vaccine in a ratio of 2:1. This study will help us to know if study vaccine works and is as safe and generates immune response for typhoid component as the licensed vaccine.

The total expected duration of your child’s participation in the study will be approximately 6 months.

The Victoria Biomedical Research Institute (VIBRI) in Kenya, together with other research partners in Western Kenya at Clinical Research sites located at Kisumu County Referral Hospital in Kisumu County and the Rachuonyo County Hospital in Homabay County being a study satellite site plan to conduct this multi-phase study following strict safety guidelines and ethical standards to monitor safety of all participants. Parents will receive detailed information about the study and will give their consent before their child can participate. Regular reactogenicity check-ups home visit, telephonically or at the clinic by study staff will ensure the children's well-being throughout the study period. If successful, this new vaccine could make a significant difference in protecting children worldwide from enteric diseases, particularly in areas where both infections are common.

Title: A Phase 2/3, Randomized, Observer-blind, Active-controlled Study to Evaluate the Safety and Immunogenicity of SII-TCV(B) in Healthy Infants and Young Children.

 

Background: Enteric fever remains a significant global health challenge, causing an estimated 11-20 million cases and 128,000-161,000 deaths annually worldwide. While WHO-prequalified typhoid conjugate vaccines are currently available, the growing burden of paratyphoid fever, particularly in endemic regions, highlights a critical gap in prevention strategies. The emergence of antimicrobial resistance and the epidemiological shift toward S. Paratyphi A further emphasizes the urgent need for a comprehensive vaccination approach.

 

Methods:This multi-phase study aims to evaluate the safety and immunogenicity of SII-TCV(B), a novel bivalent typhoid conjugate vaccine, compared to the currently licensed Typbar-TCV®. The primary objectives are to demonstrate superiority for paratyphoid A immune response while maintaining non-inferiority for typhoid-specific responses. Secondary objectives include to compare the safety and tolerability of SII-TCV(B) to Typbar-TCV®.

The study will enroll healthy infants aged 9 to <12 months, who will be randomized to receive either SII-TCV(B) or Typbar-TCV®, with concomitant administration of MR vaccine.

The study design incorporates rigorous safety and immunogenicity monitoring protocols. Trained personnel will conduct daily reactogenicity, home visit or telephonic or clinic visits for the first 7 days post-vaccination to assess immediate responses. Active surveillance for reactogenicity (solicited AEs) after vaccination will be conducted over the 7-day period (Day 1 to Day 7) by using a diary card. The surveillance for unsolicited AEs will be carried out from vaccination up to Day 29 (+14) post-vaccination by using a diary card. Surveillance for SAEs will be carried out from vaccination up to Day 181 (+30) post-vaccination. To evaluate immunogenicity, up to 5 ml of blood will be collected at pre-vaccination on Day 1, and up to 8 ml will be collected on post-vaccination on Day 29 (+14) in all participants.

Primary endpoints focus on the superiority assessment of paratyphoid A anti-LPS serum IgG immune response and non-inferiority evaluation of typhoid-specific serum anti-Vi IgG response. The study includes comprehensive safety assessments, with particular attention to both local and systemic reactions. This research represents a significant step toward developing the first bivalent vaccine offering protection against both typhoid and paratyphoid A fever, potentially addressing a critical public health need in endemic regions.

 

Conclusion: The results of this study will contribute to WHO prequalification efforts and inform future implementation strategies for comprehensive enteric fever prevention. Success could mark a significant advancement in protecting vulnerable populations against the dual burden of typhoid and paratyphoid fever.