As at 26 Mar 2021, after the first COVID-19  case was confirmed in Kenya on 12 March 2020, a total of 126,170 confirmed cases have been  identified and 2,092  people have died giving a death rate of  1.7 persons per 100 people infected.

The 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 effective 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 effectiveness 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 versions of the virus known as ‘variants’. Some examples include the ‘B1.1.7 or Alpha variant’ first discovered in the United Kingdom , the ‘B.1.351 or Beta variant’, first identified in South Africa and the ‘B.1.617 or Delta variant’ first identified in India. It is therefore important to assess whether the ability of the Moderna vaccine to prevent COVID-19 will be affected. The Moderna vaccine contains genetic material from the virus that causes COVID-19 that gives our bodies’ 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 increase immune cells that will remember how to fight the virus that causes COVID-19 if we are infected in the future. The immune cells produce substances known as 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 antibodies produced by some COVID-19 vaccines work. At this time, it is not clear whether the presence of such variants reduce how well the Moderna vaccine works to cause widespread vaccine failure. However as mentioned above, the vaccine also triggers formation of immune cells which may provide enough protection. It is also possible that the high amount of antibodies produced by the Moderna vaccine will provide enough protection despite reduced sensitivity of the South African virus.

Since the South African and Indian variant are present and increasing in the Eastern and Southern African Region, it is important to perform a study evaluating the effectiveness of the Moderna vaccine. The study will assess the impact of the vaccine developed against the original virus 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 infections 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 universally effective vaccines, or 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 virus that may have declined over time.) This study will involve people who are at high risk for COVID-19.

PLWH will be the largest group of people enrolled into the study. This is due to current insufficient scientific evidence about what vaccine schedule would best benefit PLWH.

This trial is designed as a 2- versus 3- dose vaccine regimen in participants who have never been infected with SARS-CoV-2 (Groups 1 and 3) .It will compare 2 doses versus 1 dose of vaccine in participants who had a previous infection without symptoms and have a positive SARS-CoV-2 antibody test (Groups 2 and 4).

The study aims to enroll approximately 14,000 participants, 12,600 people living with HIV and 1,400 HIV-negative participants. Among these, 5,000 participants will be confirmed to have a positive SARS-CoV-2 antibody test at screening.

At screening, participants will be grouped based on their HIV status and whether they have a positive SARS-CoV-2 antibody test that indicates previous infection or not. They will then be grouped equally and randomly in a ratio of 1:1 to either a 3-dose vs 2-dose vaccine schedule or 1-dose vs 2-dose vaccine schedule.

All participants will receive vaccine during this trial. At month 6 after enrollment, some participants will receive placebo, while some will receive vaccine. This depends on their randomization group.

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.

The B.1.617 (Delta) variant is already the dominant strain in the UK and has spread rapidly to other countries in Eastern and Southern Africa including Kenya. The Moderna mRNA vaccine has shown that the serum of vaccinated participants one week after the 2nd dose is able to neutralize the Delta variant better than the Beta variant. Whether efficacy rates will be influenced by the apparent greater infectivity of the Delta variant remains to be determined.

 New variants continue to arise (Alpha, Gamma, Epsilon, Zeta, Eta, Theta, Iota, Kappa and Lambda and it is clear that potent vaccines are needed, not only to protect the population from the medical complications of COVID-19, but also to determine if the vaccines being used are potent enough to prevent breakthrough acquisitions by multimutational variants.

The relative risks that COVID-19 poses to People living with HIV (PLWH) compared to HIV-uninfected individuals is an area of active research. It is unclear that HIV status is a significant risk factor for poor outcomes from COVID-19 disease. Some of the largest studies examining HIV status and the risk of severe COVID-19 illness have reached inconsistent conclusions.

The optimal COVID-19 mRNA vaccination regimen for PLWH is unknown. Moreover, there are no randomized controlled trials in any stage of vaccine development devoted to defining the efficacy endpoints of a COVID-19 vaccine among PLWH. PLWH are a major focus of this study given the current significant evidence gap regarding what vaccine regimens would best benefit this group. PLWH will constitute the largest proportion of the study population.

We aim to test the safety and efficacy of Moderna’s mRNA vaccine in 14,000 participants recruited from eight African countries; 300 will be recruited in Kisumu. Participants will be over age 18 years with at least one comorbidity associated with severe COVID-19, or over 18 years of age and HIV-infected.

The objective of this randomized, double-blind trial is to assess several regimens of the Moderna COVID-19 vaccine (mRNA-1273) vaccine in PLWH while differentiating between whether participants have a prior history of SARS-CoV-2 infection over 18 months. All participants will receive the vaccine. Participants will be grouped based on their HIV and SARS-CoV-2 serostatus at screening and then randomized 1:1 to either a 3-dose vs 2-dose vaccine regimen or 1-dose vs 2-dose vaccine regimen  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 only recently 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 and Delta variants of concern, as well as characterize an optimal COVID-19 mRNA vaccination regimen for PLWH.