Covid-19: The urgent, but long race for a vaccine

SARS-CoV-2, the virus which causes Coronavirus Disease 2019 (Covid-19), has been spreading rapidly globally, putting pressure on vaccine and drug developers to invent new products to stop infections and save lives.

The desperate need for a vaccine to curb the respiratory infection is driving research and development with more than 24 companies estimated to be in the race. Vaccines are entering human clinical trials much faster than ever before.

Apart from the life-saving impact of an effective Covid-19 vaccine, these new technologies and approaches are expected to also inform future scientific research on badly needed vaccines for HIV and tuberculosis.

First vaccine trial under way

In the first human clinical trial to protect against Covid-19, four volunteers were injected with a candidate vaccine in Seattle in the United States earlier this week, according to the Kaiser Permanente Washington Health Research Institute. Start-up biotechnology company Moderna Inc set a drug industry record by identifying their candidate vaccine in only 42 days after the Covid-19 virus was sequenced.

In total 45 young, healthy men and women, between 18 and 55 years, enrolled in the US National Institutes of Health-funded clinical trial. The volunteers will get different doses of the vaccine in order to establish the safety of different doses.

The objective of this first trial is only to find out if the potential vaccine called mRNA 1273 is safe and does not have any serious adverse events (side effects). If things go well, further larger trials will be conducted.

Even if all goes to plan, the vaccine will only be ready for use in 12 to 18 months.

The vaccine is made using a new process that is much faster than older methods. It doesn’t contain any part of the virus itself as is the case in most vaccines. Instead, it includes a short segment of so-called messenger RNA that is made in a lab and is designed to stimulate human cells to produce a viral protein, to which the body would develop a protective antibody response.

Other contenders

Another company called Inovio Pharmaceuticals has a DNA vaccine it says can generate protective antibodies to shield people from infection with coronavirus. Human testing of their vaccine called INO_4800 is expected to start later in 2020. Development from there is likely to follow a similar 12 to 18-month timeline.

Researchers at the Precision Vaccines Programme (PVP) at America’s Boston Children’s Hospital are on the frontline of developing a vaccine which specially targets older populations. According to the hospital’s website, the current antigen used for vaccine development is the coronavirus spike protein, named because it sits on top of the spike of a coronavirus particle. This is the part of the virus that the immune system “remembers”. Vaccine-induced antibodies, made by the immune system against the spike protein, can prevent infection.

PVP’s strategy, it says, is to combine the coronavirus spike protein with adjuvants: small molecules added to a vaccine to boost the recipient’s immune response. Adjuvants can be crucial for getting a stronger, longer-lasting, broader immune response, especially among those with weakened immunity, like the elderly.

The Gates Foundation, a major medical research funder, is spreading its bets among several cutting-edge vaccine platforms, including those using genetic material and the ones based on synthetic biology that hold promise.

Relevance for potential HIV and TB vaccines

Professor Willem Hanekom, Director of the African Health Research Institute (AHRI) in KwaZulu-Natal (KZN) said traditional vaccines have taken a long time to be developed. For example, the new M72 vaccine in development to fight TB has taken about 15 years to reach currently planned efficacy trials. The trial of the M72 subunit vaccine developed by GSK contains a fragment of the bacterium to stimulate an immune response and has been the only new vaccine, so far, showing protection against TB disease in vaccine trials.

Hanekom says the new approaches will “undoubtedly” be used in vaccine development for HIV and TB, but there are still some significant “unknowns” which complicates things. “For some viruses like Ebola and Covid-19, it may be easier to predict which proteins need to be included in the vaccine, as immune response to these proteins are likely to be associated with protection.”

As with the Moderna Inc. coronavirus candidate, he says, “you can make a piece of synthetic RNA which encodes for a protein that elicits an immune response, associated with protection”. The same, he says, could be achieved with the HI virus and the TB bacterium if “we knew which proteins are linked to protection, but we don’t have a full understanding of this at the moment”. So, while these technologies can be used it’s not as simple with HIV and TB.

For Hanekom, the number one research question is what impact Covid-19 will have on immuno-compromised South Africans. AHRI does research on prevention of HIV and TB transmission and non-communicable diseases in Somkhele, in northern KZN, which has a high HIV prevalence of 38%.

Would people with HIV do worse if infected with the novel Coronavirus?

He says surveillance needs to be done to find out. In comparison to Italy whose demographics are skewed toward older people, South Africa with a younger population may be at an advantage when it comes to Covid-19 morbidity and mortality. The WHO has said that infected elderly people are most at risk of dying as well as those with underlying chronic illnesses.

Regarding TB, Hanekom says, people with chronic lung disease are at risk of developing more severe Covid-19 disease. “We don’t yet know if people with lung disease associated with current or previous TB are at greater risk of Covid-19, but it is likely,” he said.

Heroes

Director of the Desmond Tutu HIV Centre, Professor Linda-Gail Bekker, says unlike SARS which came and went, Covid-19 is likely to be endemic and there will be a need for a vaccine in the short and long term. She said HIV is “tricky”, but new technologies are already opening up new possibilities. Johnson and Johnson’s so-called HIV mosaic concept trial is based on a synthetic approach.

Meanwhile, scientists in Australia have reported that medicines (not vaccines) to treat HIV and malaria could be used to tackle coronavirus. Infectious disease experts at the University of Queensland in Brisbane report that Chloroquine, an anti-malarial drug, and an HIV-suppressing combination lopinavir/ritonavir have both shown promising results in human tests and made the virus “disappear” in infected patients.

Bekker said a good research question would be to see if Chloroquine can be used prophylactically and as a treatment for people co-infected with HIV and the Covid-19 virus.

In addition, she said there is also discussion in South Africa on being part of the pharmaceutical company Gilead’s trial of the experimental medicine remdesivir, an intravenous treatment, which has already been used to treat an infected patient in the US. Gilead is recruiting about 1,000 patients with Covid-19 for large-scale studies in Asia, to find out whether multiple doses of remdisivir can reverse infection.

Bekker praised volunteers in current and future clinical trials for a coronavirus vaccine and treatment as “heroes”.

“We are holding our breath that all measures will flatten the infection curve. South Africa needs a break!” MC

Adele Baleta is an independent science writer, media consultant and facilitator.

This article was produced for Spotlight – health journalism in the public interest.