Lay Title: A study on the Long-Term Immunogenicity of the altSonflex1-2-3 Shigella vaccine in African children.

 

Shigellosis is an infectious disease caused by a bacteria called Shigella. Shigella is responsible for a large global burden of disease and is the leading bacterial cause of diarrheal deaths worldwide. Children under 5 years of age in low- and middle-income countries (LMICs) are most affected, particularly in the second year of life. The Global Burden of Disease 2019 estimated 148,000 deaths from shigellosis, 93,000 of which were among children under five years of age. There are no widely used licensed vaccines currently available and a Shigella vaccine is an unmet medical need. 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. This study, on the long-term immune response of the altSonflex1-2-3 vaccine, is a follow-up to two parent studies (H06_01TP/ SERU 4424) and (H06_02TP/ SERU 4829) ongoing in Kericho. These studies aim to select a dose and a preferred vaccination schedule by enrolling infants at 9 months of age and administering two or three vaccinations of a Shigella vaccine called altSonflex1-2-3 at three dose levels. The H06_04TP follow-up study will assess the long-term immune response induced by the Shigella vaccine at 1, 2 and 3 years after the last vaccination in children from both or either of the parent studies (H06_01TP/ SERU 4424 and/or H06_02TP/ SERU 4829) at the selected dose level from the H06_01TP/ SERU 4424 study. Parents/legally acceptable representatives of participants who enrolled in either of the parent studies in Kericho and provided consent to participate in follow-up studies will be contacted and will be asked if their child could participate in this current study. Only participants who received a complete series of Shigella (altSonflex1-2-3) or control vaccines will be enrolled. No vaccinations are planned in this study, and blood samples for immunogenicity will be collected at 12, 24 and 36 months after participants’ last vaccination in the parent protocol. A maximum of 179 participants will be enrolled and followed up for 24 months. This study could indicate if, and when a booster vaccine might be needed and eventually provide information regarding the expected duration of protection against shigellosis. 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, Walter Reed Army Institute of Research Institutional Review Board and Kenya’s Ministry of Health.

ABSTRACT

Shigella is responsible for a large global burden of disease and is the leading bacterial cause of diarrheal deaths worldwide. Children under five years of age in low- and middle-income countries (LMICs) are the most affected, particularly in their second year of life. According to the Global Burden of Disease 2019, Shigella was responsible for an estimated 148,000 deaths, 93,000 of which occurred among children under five years of age. Currently, there are no widely used licensed vaccines available making Shigella vaccine an unmet medical need. Treatment for shigellosis is mainly supportive, aiming to stabilize patients and restore lost electrolytes due to diarrhea. Cases of moderate to severe diarrhea may become persistent and may warrant antibiotic treatment. However, increasing rates of antibiotic resistance among Shigella serotypes around the world pose a significant challenge to current drug therapies. Thus, prevention of diarrheal diseases caused by Shigella, with the introduction of an efficacious vaccine, is important. This study is a long-term follow-up to two studies (H06_01TP/ SERU 4424) and (H06_02TP/ SERU 4829). The primary aims of these studies is to select an appropriate dose and preferred vaccination schedule by enrolling infants at 9 months of age and administering two or three doses of the GVGH Shigella 4-component candidate vaccine (altSonflex1-2-3) at three dose levels.

This current study (H06_04TP) is a phase 2, open-label, single-center study. It will assess the longevity of the immune response induced by the altSonflex1-2-3 candidate vaccine at 1, 2 and 3 years after the last vaccination in children from both or either of the parent studies (H06_01TP/ SERU 4424 and/or H06_02TP/ SERU 4829) at the selected dose level from the H06_01TP/ SERU 4424 study. Parents/legally acceptable representatives of eligible participants from the parent studies conducted in Kericho who previously consented to participate in follow-up studies will be contacted and asked if their child could participate in this H06_04TP study. Participants who received a complete series of altSonflex1-2-3 or control vaccines will be enrolled into H06_04TP study. No vaccinations are planned in this study, only blood samples will be collected for immunogenicity assessment at 12, 24 and 36 months after participants last vaccination in the parent protocol. A total of 179 participants who meet the eligibility criteria will be enrolled and followed for 24 months. Establishing the longevity of the immune response to altSonflex1-2-3 vaccine in this study may help determine if, and when a booster dose might be necessary and evaluate its potential ability to provide long-term clinical protection against shigellosis. 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, Walter Reed Army Institute of Research Institutional Review Board and Kenya’s Ministry of Health.