Purpose To evaluate the effectiveness and safety of the single dose Ad26.COV2.S (Jansen)
COVID-19 vaccine plus a homologous boost with Ad26.COV2.S (Janssen) COVID-19 vaccine
among Sisonke participants as compared to unboosted Sisonke participants

In addition the investigators will continue to evaluate VE of the Sisonke Boost compared
to:

i) Vaccinated populations pre boosts ii) Unvaccinated populations in South Africa.

Study design Open-label, single-arm phase 3B vaccine implementation study

Rationale South Africa is severely affected by the global COVID-19 epidemic, and
following the initial prime vaccination among HCWs in the first 4 months of 2021. New
data has demonstrated the safety and effectiveness of a booster dose given two months or
more after the initial Ad26.COV2.S. This provides the rationale and feasibility for the
evaluation of a homologous booster vaccine dose to the cohort of vaccinated Sisonke
participants to inform the larger vaccine rollout.

Study participants Sisonke participants age 18 and over working in the South African
public and private health care sector (approx N=500 000) who were enrolled in Sisonke and
have not subsequently had a further booster vaccine dose.

Study sites Department of Health Vaccine Administration Sites across South Africa
supported by the Sisonke (Together) (VAC31518COV3012) Trial Research Site Investigators
and Study Staff

Study duration Participants will receive a homologous Ad26.COV2.S (Janssen) booster dose
of vaccine at least 6 months post the prime vaccination. The investigators will monitor
outcomes utilising the DATCOV surveillance system and NHLS/NICD SARS COV-2 testing
databases for up to 2 years post initial vaccination.

Study products Ad26.COV2.S by Janssen administered as a single dose followed by a single
booster injection.

Primary objectives • To assess the effectiveness of Ad26.COV2.S vaccine as a homologous
boost on severe COVID, hospitalizations and deaths in Sisonke participants as compared
with the unboosted Sisonke populations.

Secondary objectives To assess the effectiveness of Ad26.COV2.S vaccine as a homologous
boost on severe COVID, hospitalizations and deaths in Sisonke participants as compared
vaccinated and unvaccinated populations of essential workers in South Africa.

- To estimate the incidence of symptomatic SARS CoV-2 infections in Sisonke
participants following a boost compared with the unboosted Sisonke populations and
general vaccinated and unvaccinated population in South Africa

- To estimate booster dose uptake among Sisonke participants in South Africa

- To monitor the genetic diversity of breakthrough SARS CoV-2 infections.

- To monitor safety in the case of homologous boosts in Sisonke participants.