Since 12 March 2020 when the first COVID-19 case was confirmed in Kenya, as at 26 Mar 2021, a total of 126,170 confirmed cases have been identified and 2,092 people have died yielding a death rate of 1.7 persons per 100 people infected. The mRNA vaccine developed by Moderna and based on the genetic information of the orignal viral strain that originated in Wuhan, China, was proven to be highly efficacious in preventing COVID-19 infections. It received an Emergency Use Authorization by the Food & Drug Administration and is now widely used in the USA but has not been used in the African continent. The Africa CDC has encouraged nations in its continent to test the efficacy and safety of a variety of vaccines in their populations. As SARS-CoV-2 – the virus that causes COVID-19 – spreads around the globe, it is mutating. It changes in response to the different immune responses in different people. It changes to form new variants for example the B1.1.7 variant first discovered in the United Kingdom and the B.1.351, first identified in South Africa. It is therefore important to assess whether the ability of the Moderna mRNA vaccine to prevent Covid 19 will be affected. The Moderna mRNA vaccine contains material from the virus that causes COVID-19 that gives our cells instructions for how to make a harmless protein that is unique to the virus. After our cells make copies of the protein, they destroy the genetic material from the vaccine. Our bodies recognize that the protein should not be there and build T-lymphocytes (a type of white blood cell) and B-lymphocytes that will remember how to fight the virus that causes COVID-19 if we are infected in the future. The B lymphocytes produce substances known as neutralizing antibodies which can stop a virus from infecting the body by affecting how the molecules on the virus’ surface can enter cells in the body. The SARS-CoV-2 South African variant has changes known to reduce how well the neutralizing antibodies produced by the Moderna mRNA vaccine work. At this time, it is not clear whether this can reduce how well the vaccine works and cause widespread vaccine failure. However as mentioned above, the vaccine also triggers formation of T lymphocytes which may provide enough protection. It is also possible that the high amount of neutralizing antibodies produced by the Moderna mRNA vaccine will provide enough protection despite reduced sensitivity of the South African virus. Since the South African variant is present and increasing in the Eastern and Southern African Region, it is important to perform a vaccine efficacy study. The study will assess the clinical impact of the parent mRNA vaccine (i.e., original Wuhan strain) on both moderate and severe disease and death in these regions among adults who are at high risk of severe disease. The study will also carefully examine breakthrough viruses in fully vaccinated individuals. A breakthrough infection is a case of illness in which a vaccinated individual becomes sick from the same illness that the vaccine is meant to prevent. This is important so as to determine whether vaccines need to be tailor made for the different variants of concern or if vaccines need to be modified to accommodate changes for global vaccines, and whether the original vaccine will provide higher protection against severe disease when administered as a booster. (A booster dose is an extra administration of a vaccine after an earlier dose. It is intended to increase immunity after memory against a foreign substance eg. a virus has declined through time). This study will involve people who are at high risk for COVID-19. This trial has an immediate vs. delayed design, eventually immunizing all participants with the vaccine but delaying by three months (at the crossover visit) the immunization of half of participants to assess the efficacy of the mRNA vaccine. Fourteen thousand participants will be recruited from eight African countries, with approximately three hundred from the Kisumu Clinical Research Site. Although a great deal is known about the safety of the Moderna vaccine in the US, this trial will provide an opportunity to test the vaccine’s safety in African populations.

SARS-CoV-2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has evolved into new strains that are also referred to as ‘variants.’ A rapidly spreading variant called B.1.351, first identified in South Africa has now spread to Kenya. This variant is considered a ‘variant of concern’ because it is more transmissible than the original strain and because some vaccines appear to have reduced protection against this strain of SARS-CoV-2. In vitro, the B.1.351 variant’s mutations reduce efficiency of neutralizing antibodies induced by the Moderna mRNA (original Wuhan strain) vaccine. It is unknown whether this in vitro finding also reduces the clinical efficacy of the vaccine. We aim to test the safety and efficacy of Moderna’s two-dose mRNA vaccine in 14,000 participants recruited from eight African countries; 300 will be recruited in Kisumu. Participants will be over age 40 years with at least one comorbidity associated with severe COVID-19, or over 18 years of age and pregnant, or over 18 years of age and HIV-infected. The objectives of this randomized, double-blind, immediate versus deferred vaccination trial with cross-over at approximately three months are to assess vaccine efficacy to prevent virologically confirmed or virologically unconfirmed symptomatic COVID-19. All participants will receive the vaccine. The ratio of participants in immediate and deferred arms is 1:1. CDC Africa encouraged testing various vaccines in the continent to be sure they are efficacious. The World Health Organization has recently listed the Moderna vaccine for emergency use listing. To date, mRNA vaccines have hardly been deployed in the African continent. If this trial is successful, it will provide a new weapon to control the pandemic in Africa and yield critical information on its efficacy against the new variants emerging in Kenya, including the B.1.351 variant of concern.