The Coronavirus (COVID-19) emerged in the human population in Wuhan City, Hubei Province, China in December 2019. The burden of COVID-19 illness and death has been very bad with more than 3.1 million deaths, over 151 million confirmed cases worldwide, including more than 163,620 cases and 2,907 deaths in Kenya as of 10 May 2021. The COVID-19 disease has caused major social, educational and economic disruptions. Despite public health measures of isolation, quarantine, social distancing, and handwashing to stop the spread of the virus, and the rapid development and worldwide use of COVID-19 vaccines, the worldwide burden of coronavirus infections and disease remains substantial, showing the need for safe and effective vaccines across all countries including in Africa.

New, easy to transmit types of coronavirus have emerged and are spreading worldwide. These include the Alpha variant called B.1.1.7 seen initially in the UK, the Beta variant (B.1.351) seen initially in South Africa, the Gamma variant (P.1) seen initially in Brazil and the Delta variant (B.1.617) seen initially in India. All these variants have since spread and been detected in many other countries around the world. A key question is whether currently approved and available COVID-19 vaccines will be able to protect against infection or disease from these variants. Early study data using the Novavax vaccine and the Astra-Zeneca/Oxford University vaccine have showed lower effect against COVID-19 in South Africa where the B.1.351 is common compared to the effect observed for these vaccines in studies conducted in the UK. However, results from the Janssen vaccine against COVID-19 disease in South Africa shows that the vaccine gives some protection against the B.1.351 variant.

To address the urgent medical need caused by this outbreak, Sanofi is developing a vaccine from the coronavirus protein. The Sanofi study called VAT00008 will be a Phase 3, carried out in multi- centers, in several countries. It will be done in adults 18 years of age and older to assess if the vaccine works, if it is safe and able to help our bodies protect us from the coronavirus. The study will have a vaccine with one type of the virus (monovalent) and another vaccine with 2 types of the virus (bivalent). The study is designed to show if the Sanofi coronavirus vaccines (monovalent and bivalent) is able to prevent the occurrence of COVID-19 disease from at least 14 days after the second injection of the vaccine in individuals who have not previously had COVID-19. COVID-19 virus will be tested in the laboratory among people who have COVID-19-like illness.

Participants will in 2 groups including those who have previously been infected with coronavirus and those who have not been infected before based on laboratory tests. A total of about 21 046 participants are planned to be enrolled (5080 per study vaccine group in Stage 1 and 5443per study vaccine group in Stage 2). For each stage, participants who have previously been infected with coronavirus will be approximately 30%of the total study population. The trial will target recruitment of people of different races and tribes that at a minimum will represent the countries in where the trial will be conducted. The goal of this study is to generate results required for approval of each of the vaccines for  use in  prevention  against coronavirus infection and disease in adults. The results collected during this study will also support future development of the vaccine in other populations for example children and pregnant women.

Background
SARS-CoV-2 is a novel coronavirus that emerged in the human population and has led to a pandemic of acute respiratory disease named COVID-19. The burden of SARS-CoV-2
morbidity and mortality has been catastrophic with greater than 2.8 million deaths recorded since first emerging in December 2019 among over 131.9 million confirmed cases
(as of 06 April 2021) (2). In many locations, the rapid emergence of COVID-19 has overwhelmed the capacity of health systems to provide care for COVID-19-affected
patients, let alone unaffected patients. Interventions to reduce transmission through reduction of population contact (also called social distancing) has had profound
economic consequences. Safe and effective vaccines with sufficient supply would be vital to address the significant medical and societal burden caused by the pandemic.
The CoV2 preS dTM-AS03 vaccines developed by Sanofi Pasteur utilize a recombinant protein approach in combination with an oil-in-water adjuvant, AS03 provided by
GlaxoSmithKline (GSK). The CoV2 preS dTM-AS03 vaccines belong to the pharmacotherapeutic group of “covid19 vaccines”. The vaccines contain recombinant S protein,
stabilized to maintain native prefusion trimer configuration as present on the viral envelope. The purpose of the study is to assess the efficacy, safety, and immunogenicity of
two CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) in adults 18 years of age and older in a multi-stage approach.
Methods
This study is designed to maximize representation of the broader population by minimizing exclusionary eligibility criteria and allowing the participation of individuals with a
broad range of medical conditions, including controlled HIV infection, Hepatitis B and Hepatitis C, and conditions associated with an increased risk of severe COVID-19. It is
also designed to be inclusive of other subpopulations affected by COVID-19, including older adults as well as ethnic and racial minorities. Participants will be screened for
eligibility criteria at the time of inclusion and then randomized to either the investigational vaccine or placebo in a 1:1 ratio in each stage. • Stage 1: eligible participants will
be randomized to receive either 2 injections of CoV2 preS dTM-AS03 (D614) vaccine or Placebo 1 (participants who receive the placebo as part of Stage 1) administered 21
days apart • Stage 2: eligible participants will be randomized to receive 2 injections of either CoV2 preS dTM-AS03 (D614 + B.1.351) vaccine or Placebo 2 (participants who
receive placebo as part of Stage 2) administered 21 days apart. Randomization will be stratified by age groups (18-59 years of age and 60 years of age and older), baseline
SARS-CoV-2 rapid serodiagnostic test positivity, and site. In the event that the enrollment in Stage 1 overlaps with enrollment of Stage 2, participants will continue to be
randomly allocated to one of the investigational vaccine groups and their matched placebo group in a 1:1 ratio.
Approximately 37 430 participants are planned to be enrolled (8000 per study intervention group in Stage 1 and 10 715 per study intervention group in Stage 2)The duration
of the study for each participant will be 365 days post-last injection (ie, approximately 386 days total). The study includes 8 visits at D01, D22, D43, D78, D134, D202, D292,
and D387. Participants will be contacted once a week over the entire duration of the study to inquire about the development of symptoms of COVID-19-like-illness and to
remind participants to contact study staff if they experience symptoms of COVID-19-like illness. Additional visits and procedures are included for participants with verified
COVID-19-like illness.