Lay Title: A study on the safety and immune responses to the GVGH vaccine against shigellosis in infants

Shigellosis is an infectious disease caused by a group of bacteria called Shigella. Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death. There is presently no widely available vaccine against Shigella. Treatment for shigellosis is mainly supportive to keep patients stable. Shigellosis can be treated with antibiotics but many Shigella bacteria no longer respond well to or are resistant to most of the used antibiotics. Thus, a very important way to fight Shigella is through prevention with the use of vaccination.. The aim of the study is to assess how an experimental Shigella vaccine, called altSonflex1-2-3, given in two doses, makes the body to produce proteins that fight off the bacteria causing shigellosis and to assess the side effects the vaccine may cause. Infants who are 9 months old will receive 2 injections of Shigella vaccine or 2 injections of the control vaccines. The benefits of this study include, participants or participants’ parents may gain medical advice about their own or their children’s health status H06_02TP /WRAIR # /KEMRI/SERU/CCR/0327/4829 Kericho Site Specific Addendum Version 2.0 dated 15 Nov 2023 Page 7 of 30 through the medical evaluations and laboratory assessments associated with the study. Vaccines administered as control and not routinely given will be provided free of charge and can provide protection against Salmonella Typhi, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b. The infants who will be assigned to receive the shigella vaccine will receive THYPIBEV vaccine after the study is completed as a benefit. The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine.

Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally and, with 15.2%, it ranked second with regard to pathogen contributions in global diarrheal deaths. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death. There is presently no widely available vaccine against Shigella. The candidate vaccine, altSonflex1-2-3, has been evaluated for the FTiH in adults in Belgium, and is currently evaluated in a Phase 2 age de-escalation clinical study in Kenya, with the aim of identifying a preferred dose, using a 3-dose vaccinations schedule in infants from 9 months of age (NCT05073003). The current Phase 2 clinical study will evaluate the immunogenicity and safety of an alternative 2-dose vaccination schedule. The candidate vaccine, altSonflex1-2-3, will be administered intramuscularly by study site staff and contains 15 μg (Dose C), 7.5 μg (Dose B), or 3.75 μg (Dose A) of OAg for each antigen component. About 400 9-month old infants will be screened to enroll 200 participants. The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine. The study findings will be shared with all authorities having oversight of this protocol including the sponsor, Kenya Medical Research Institute Scientific Ethics Review Unit, Pharmacy and Poisons Board, Walter Reed Army Institute of Research Institutional Review Board and Kenya’s Ministry of Health.