Yellow fever is a viral disease spread by a mosquito during the rainy season. This disease is widespread in the tropical and subtropical areas in South America and Africa. The important prevention measure is vaccination. There are other approved vaccination for YF but the uptake is not satisfactory as a result of vaccine shortage, this is because the available vaccines stocks are sidetracked to preventive campaigns which has affected the supply of this vaccine to the immunization program and the global supply for travelers too. WHO reports a total of 47 countries, including 34 from Africa and 13 from Central and South America; YF is widespread in these regions.. As per WHO, the estimated number of serious cases in both continents is 84,000-170,000, with approximately 29,000-60,000 deaths annually. The outbreaks are necessitating an urgent response. There are a limited number of manufacturers of YF vaccine. In such an event, a global shortage of YF vaccine is not uncommon. This has given rise to evaluation of measures to counter this shortage such as fractional dosing of YF vaccines. The vaccine supply is still a major obstruction; these low YF vaccination coverages indicate the presence of populations facing the danger of YF and a danger of continued transmission. Hence, SIIPL has developed this Yellow Fever Vaccine to address this issue of   YF vaccine shortage. SIIPL has developed a YF vaccine which contains the same 17D-213 vaccine strain used in already licensed and WHO prequalified vaccines. The objective of this study is to demonstrate that the immune responses generated by SII-YFV are equal or more effective as compared to STAMARIL^® .The study will be conducted in Kenya at the KEMRI CRDR Clinical Research Annex- Nairobi. The expected study duration is approximately 24months, individual participation will be approximately 7months. Healthy male or female volunteers aged ≥ 1 to < 60 years will be divided into three age groups of ≥ 1 to < 10 years, ≥ 10 to < 18 years and ≥ 18 to < 60 years and into the immunogenicity and reactogenicity cohort for the three age groups. They will be randomized in the ratio of 3:2 to receive the allocated either SII-YFV or STAMARIL. A total of 2280 participants will be enrolled in to the study in Kenya; Nairobi site will recruit at least 1140 participants. A single dose of either SII-YFV or STAMARIL^® will be administered subcutaneously to the study participants. There will be three scheduled visits during the study.  A screening and vaccination visit (Day 0) followed by additional study visits on Day 28 and on Day 180 post-vaccination. Prior to enrolment participants will be taken through consenting and will sign assent/consent as applicable; only eligible participants will be enrolled into the study. The results of this study will support prequalification by the WHO for global application. This will improve YF vaccination coverages and reduce contact of populations at danger of YF and a risk of continued transmission.

Background: Yellow fever (YF) is a viral disease transmitted by a mosquito; the Aedes aegypti and Haemagogous species mosquitoes, during the rainy season. This disease is endemic in the tropical and subtropical areas in South America and Africa.  Vaccination is the most important means of preventing the infection. There are other approved vaccines for YF but the uptake has not been adequate due to vaccine shortage as a result of available vaccine stock being diverted to preventive campaigns; this has significantly affected the supply to immunization programs and the global supply for travelers too. WHO reports a total of 47 countries, including 34 from Africa and 13 from Central and South America, endemic for YF. As per WHO, the estimated number of severe cases in both continents is 84,000-170,000, with approximately 29,000-60,000 deaths annually. The outbreaks are necessitating an urgent response. In such an event, a global shortage of YF vaccine is not uncommon. This has given rise to evaluation of measures to counter this shortage such as fractional dosing of YF vaccines.

Purpose and rationale: The vaccine supply is still a major obstruction These low YF vaccination coverages indicate the presence of an underlying susceptible population at risk of YF and a risk of continued transmission. Hence, SIIPL has developed this Yellow Fever Vaccine to address this issue of yellow fever vaccine shortage. SIIPL has developed a Yellow Fever vaccine which contains the same 17D-213 vaccine strain used in already licensed and WHO prequalified vaccines.  

Objective: To demonstrate the non-inferiority of the immune responses generated by SII-YFV compared to STAMARIL^® in terms of YF neutralizing antibody (NAb) seroconversion rates as determined by plaque reduction neutralization test (PRNT₅₀).

Methodology: The study will be conducted in Kenya at the KEMRI CRDR Clinical Research Annex- Nairobi. The expected study duration is approximately 24months, individual participation will be approximately 7months. Healthy male or female volunteers aged ≥ 1 to < 60 years will be divided into three age groups of ≥ 1 to < 10 years, ≥ 10 to < 18 years and ≥ 18 to < 60 years and into the immunogenicity and reactogenicity cohort for the three age groups. They will be randomized in the ratio of 3:2 to receive the allocated IP. A total of 2280 participants will be enrolled; Nairobi site will recruit at least 1140 participants. A single dose of either SII-YFV or STAMARIL^® will be administered subcutaneously to the study participants. There will be three scheduled visits during the study.  A screening and vaccination visit (Day 0) followed by additional study visits on Day 28 and on Day 180 post-vaccination. Prior to enrolment participants will be taken through consenting and will sign assent/consent; only eligible participants will be enrolled into the study.

Expectation: The current Phase III study is designed to demonstrate the non-inferiority in terms of the seroconversion rates achieved with SII YF vaccine versus STAMARIL. This study will support prequalification by the WHO for global application. This will improve YF vaccination coverages and reduce susceptibility of populations at risk of YF and a risk of continued transmission.