The University of the Witwatersrand (Wits) is undertaking a second Covid-19 vaccine clinical trial, led by Wits University Vaccinology Professor Shabir Madhi. Wits will begin screening participants for the NVX-CoV2373 trial from August 17.

Madhi motivated vaccine producer US biotech company Novavax to undertake a domestic trial of the vaccine as part of a second phase of evaluating if the nanoparticle S-protein in the Covid-19 vaccine known as NVX-CoV2373, protects against Covid-19 disease in adults aged between 18 and 64 years old.

Novavax is a late-stage biotechnology company that develops next-generation vaccines for serious infectious diseases.

Madhi previously collaborated with Novavax as a lead investigator on the RSV vaccine for pregnant women, which aimed to prevent the most common cause of pneumonia in babies.

The Phase 2 NVX-CoV2373 study in South Africa will enrol about 2 900 volunteers aged between 18 and 64 years old. The trial will evaluate the vaccine candidate’s safety, immunogenicity and efficacy – protection against Covid-19.

“The major motivation for Covid-19 vaccines being evaluated at an early stage in South Africa is to generate evidence in the African context on how well these vaccines work in settings such as our own,” says Madhi.

“This would enable informed decision-making when advocating for the adoption of this [NVX-CoV2373 vaccine candidate] or other Covid-19 vaccines in African countries, once they are shown to be safe and effective.”

Further participating in the clinical development of these vaccines at the outset will assist in advocating for South Africans to be among the first in line to access these life-saving vaccines, once they become available, he says.

Madhi, who is the executive director of the South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Vida) at Wits and the Faculty of Health Sciences Dean-elect, also leads the South African Ox1Cov-19 Vaccine Vida trial launched on June 23, in association with University of Oxford and the Jenner Institute.

The Novavax vaccine in the South African trial leverages technology used successfully to develop vaccines against influenza virus and experimental vaccines against Ebola and respiratory syncytial virus.

The Novavax NVX-CoV2373 vaccine candidate is engineered from the genetic sequence of Sever Acute Respiratory Syndrome‑CoV‑2, the virus that causes Covid-19 disease.

The randomised, observer-blinded, placebo-controlled Phase 2 clinical trial in South Africa will include two cohorts, one evaluating the efficacy, safety and immunogenicity of NVX-CoV2373 in about 2 650 healthy, HIV-negative adults. 

The second cohort will evaluate the safety and immunogenicity of NVX-CoV2373 in about 240 medically stable, HIV-positive adults.

In preclinical studies, NVX‑CoV2373 demonstrated the elicitation of antibodies that block the binding of spike protein to receptors targeted by the virus – this is a critical aspect for effective vaccine protection.

Studies of this Novavax vaccine in non-human primates have shown protection against SARS-Cov-2 infection in upper airways (nasal passages), as well as protection against lower airway (lung) disease.

Safety and immunogenicity (the ability of a foreign substance, such as an antigen, to provoke an immune response) data from part 1 of the Novavax Phase 1/2 randomised, observer-blinded, placebo-controlled trial of its Covid‑19 vaccine with and without Matrix‑M adjuvant in healthy adults aged between 18 and 59 years old, conducted in Australia, have been submitted to the US Food and Drug Administration and an independent safety monitoring committee.

In the Phase 1 clinical trial, NVX-CoV2373 was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera. The data has been submitted for peer review to a scientific journal and are available online.

Novavax president and CEO Stanley Erck says this important Phase 2 clinical trial will not only provide additional data on safety and immunogenicity of NVX-CoV2373, but also has the potential to provide an early indication of efficacy, as South Africa is experiencing a surge of Covid-19 infections.

The Bill & Melinda Gates Foundation awarded Novavax a $15-million grant towards the Covid-19 vaccine efficacy trial in South Africa.

The South African study is part of a larger, global clinical programme to evaluate NVX-CoV2373, including larger Phase 3 studies with about 30 000 participants, to be launched throughout the world.