Category: COVID

SAMA Head Urges Stronger Lockdown; Two-thirds of Cases in Gauteng

Photo by Maxim Zhgulev on Unsplash

The South African Medical Association (SAMA) had said that early indications showed that the third wave of South Africa’s COVID pandemic would be worse than the previous two.

As infections surge around the country, particularly in Gauteng Province, the government  moved to Level 3, strengthening some curbs, including liquor sale restrictions, an extended curfew and a cap on the number of people allowed at gatherings. However, there has been no outright ban on alcohol.

As of Thursday, 11767 new COVID infections have been confirmed, with nearly two-thirds (7502) being recorded in Gauteng. The overall case positivity rate is 22.6%

SAMA chairperson Dr Angelique Coetzee said that the government’s measures were implemented far too late.

“People carry on as if everything is right. Everything is not right. We are in a pandemic, we are in a third wave and a third wave that’s going to be worse. At this stage, all the indications are that it is going to be worse than the second wave.”

Speaking to the SABC, she said Gauteng was running out of beds and oxygen. “If you want a bed in Gauteng you are going to struggle so this is what we’re seeing and if we want to get out of this we need to make tough decisions. But it seems like it’s not going to happen so for now it is what it is and no one should be astonished if the numbers go up,” says Coetzee.

Dr Coetzee also warned that allowing schools to remain open was a bad decision.

“Without proper, effective and decisive measures to curb the spread of COVID, our infection and fatality numbers are going to climb even further. In addition, schools are still open, travel is still allowed and public transport can still operate as they currently are. This should not have been allowed.”

The Basic Education Department had already dismissed suggestions that schools should be closed as well as part of the COVID containment efforts. She also argued against a  simple tightening of curfews and alcohol sales.

“Nothing significant has changed. The stricter curfew measures and limitations on alcohol sales will simply mean people change their behaviour to accommodate for these restrictions and will have little impact on people’s daily routines. This is actually where restrictions should have been targeted.”

Speaking to Jacaranda, she said, “For us, it doesn’t make sense, we need people at home. We don’t want people in a shopping centre or anywhere else, if we can manage to do that for three to four weeks we can get the numbers down but for now, I don’t see that happening.”

Source: EWN

Inhaled Corticosteroid Could Shorten Moderate COVID

Source: Pixabay

Early treatment with inhaled budesonide shortens recovery time by a median of three days in community-treated patients with COVID who are at higher risk of more severe illness, according to preliminary results from an Oxford University trial.

Inhaled budesonide is a safe, fairly cheap and readily available corticosteroid commonly used in inhalers for the treatment of asthma and chronic obstructive pulmonary disease

Based on an interim analysis using the latest data from 25th March 2021, the results showed the estimated median time to self-reported recovery for inhaled budesonide was three days shorter compared to usual care, with a high probability of being superior to the usual standard of care. Of those taking inhaled budesonide, 32% recovered within the first 14 days and stayed well until the 28 day endpoint, compared to 22% receiving usual care. Budesonide group participants also reported greater wellbeing after two weeks. 

Among patients who had completed the study, 8.5% (59/692) in the budesonide group were hospitalised with COVID compared with 10.3% (100/968) in the usual care group, with an estimated percentage benefit of 2.1%. However as fewer than expected people were admitted to hospital in the trial, and with COVID cases falling in the UK, it is not clear from this interim analysis whether budesonide reduces hospitalisations.

Patients with COVID symptoms that started within 14 days and who are at higher risk of a poor outcome from the illness were eligible to join the trial and those who tested positive for SARS-CoV-2 were included in the main analysis. Patients receiving inhaled budesonide were asked to inhale 800 micrograms twice a day for 14 days, with a 28 day follow-up.

Joint Chief Investigator, Professor Chris Butler, a South Wales GP and Professor of Primary Care from the University of Oxford’s Nuffield Department of Primary Care Health Sciences, said, “PRINCIPLE, the world’s largest platform trial of community-based treatments for COVID-19, has found evidence that a relatively cheap, widely available drug with very few side effects helps people at higher risk of worse outcomes from COVID recover quicker, stay better once they feel recovered, and improves their wellbeing. We therefore anticipate that medical practitioners around the world caring for people with COVID in the community may wish to consider this evidence when making treatment decisions, as it should help people with COVID recover quicker.”

When the data has been obtained and analysed, detailed results on time to recovery and hospitalisations will be published. The full pre-print is available on the MedRxiv server.

Source: University of Oxford

A Common Cold Virus Could Stifle COVID

Photo by Kelly Sikkema on Unsplash

There might be an unexpected benefit to the rhinovirus, or the most frequent cause of the common cold — protection against COVID, according to a study at Yale University.

Around 200 viruses cause the common cold, of which rhinovirus is the most common. Researchers found that the rhinovirus kick-starts interferon-stimulated gene activity. Within airway tissues infected with the rhinovirus, this also can halt replication of the SARS-CoV-2 virus.

Setting off these defences early in the course of COVID infection might prevent or treat the infection, said Ellen Foxman, assistant professor of laboratory medicine and immunobiology at the Yale School of Medicine and senior author of the study. One method is treating patients with interferons, an immune system protein which is also available as a drug.

“But it all depends upon the timing,” Prof Foxman clarified.

In later stages of COVID, high interferon levels correlate with worse disease and may fuel overactive immune responses, according to previous research. But recent genetic studies show that interferon-stimulated genes may actually also be protective in cases of COVID infection.

Prof Foxman’s lab wanted to study this defence system early in the course of COVID infection.

Earlier studies by the lab had shown that common cold viruses may protect against influenza, so they decided to find out whether rhinoviruses would have the same beneficial impact against the COVID virus. The researchers infected lab-grown human airway tissue with SARS-CoV-2 and found that for the first three days, viral load in the tissue doubled about every six hours. However, replication of the coronavirus was completely halted in tissue which had been exposed to rhinovirus. When antiviral defences were blocked, the SARS-CoV-2 could replicate in airway tissue previously exposed to rhinovirus.

The same defences slowed down SARS-CoV-2 infection even without rhinovirus, but only with a low infectious dose, suggesting that the viral load at the time of exposure affects whether the body can effectively fight the infection.

The researchers also studied nasal swab samples from patients diagnosed close to the start of infection. They found evidence of rapid growth of SARS-CoV-2 in the first few days of infection, followed by activation of the body’s defenses. According to their findings, the virus typically increased rapidly for the first few days of infection, before host defenses kicked in, doubling about every six hours; in some patients the virus grew even faster.

“There appears to be a viral sweet spot at the beginning of COVID, during which the virus replicates exponentially before it triggers a strong defence response,” Foxman said.

Interferon treatment is promising but could be tricky, she said, because it would be mostly effective in the days immediately after infection, when many people are asymptomatic. In theory, interferon treatment could be used prophylactically in people at high risk who have been in close contact with others diagnosed with COVID. Interferon is being trialled in COVID, and there appears to be a benefit when given early, but not late.

The study helps explain why influenza infections are lowered at times of the year when the common cold is prevalent, Prof Foxman said. The easing of social distancing measures could cause the common cold and flu viruses, which have been suppressed, to spring back with greater force. Respiratory viruses interference with each other could be a mitigating factor, creating an ‘upper limit’ on the degree to which respiratory viruses circulate together, she said.

“There are hidden interactions between viruses that we don’t quite understand, and these findings are a piece of the puzzle we are just now looking at,” Prof Foxman said.

Source: Yale University

Journal information: Cheemarla, N.R., et al. (2021) Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal of Experimental Medicine.doi.org/10.1084/jem.20210583.

Tougher Restrictions for Gauteng Being Debated

Image by Quicknews

As COVID cases continue to rise virtually unabated by the move to Level 2 lockdown, there are reportedly discussions at the National Coronavirus Command Council to tighten the lockdown restrictions.

The Gauteng government wants the province to have tighter lockdown restrictions, as it is host to about half of daily new infections of COVID in the country. Despite the high infection rate in the province, many in Gauteng are against tougher restrictions, such as the Gauteng Education Department and South African Council of Churches. Acting Health Minister Mmamoloko Kubayi-Ngubane says that she will speak to the National Coronavirus Command Council about the issue.

The province’s premier David Makhura said the province is asking for increased measures. “Level 2 as we know it currently is not having a sufficient impact,” he said. “People are going on as if we are really not in the middle of a raging pandemic.”

With Charlotte Maxeke Academic Hospital being indefinitely closed, the pressure is mounting on both public and private facilities which running out of ICU beds.

“So, we talk to the private hospitals almost on a daily basis, and they do indicate to us that they are running almost at about 80% of their capacity for ICU. In the public hospitals, we are also running at about 70%,” said Thabo Masebe, communications head of the Gauteng government.

He confirmed that the province was looking for tougher restrictions to curb new infections.

“That’s what the premier had said. He will be raising that with national government to see what added restrictions could be made to help slow down the rate of infections in the province,” Masebe said.

Source: ENCA

Drop in Heart Attacks Linked to COVID Pandemic

Photo by camilo jimenez on Unsplash

A sharp drop in heart attacks in Finland last year seems to be a result of the COVID pandemic, doctors believe.

Cardiologist Mika Laine noticed a roughly 30 per cent reduction in the number of patients suffering myocardial infarction at Helsinki University Central Hospital in April and May 2020. But what was even more surprising was that this was not an isolated occurrence.

“When we started to study this further, we noticed that exactly the same phenomenon happened everywhere else in Finland and also in other countries in Europe and in the United States. So it was a kind of global phenomenon that happened during the COVID pandemic,” he told Euronews.

What was behind the drop?

Dr Laine is of the opinion that the fall in heart attack patient numbers results from changes made in response to the COVID outbreak.

“We have the exact same genes that we had a year ago, two years ago. So it has to be something in the environment that has changed,” he said. One major factor could be the massive global shift to remote working for many people, as a result of the lockdowns.

“People are at home, they are less stressed because they don’t need to go through morning traffic, hurry to work and so forth,” Dr Laine added.

EU Science Hub data shows that even before the pandemic, Finns worked remotely more than almost any other EU country. Last May, EU labour research body Eurofound revealed that Finnish workers made the fastest switch to teleworking in the EU, with nearly 60 per cent switching over.

“We also see this decrease in those people who are retired, who don’t go to work, so it cannot be just because you’re commuting,” said Dr Laine.
He however cautioned that there could be other factors behind the fall in heart attack patients.

Was there a real fall in heart attacks in 2020?

“We know that many people stopped smoking because smoking was associated with severe COVID mortality,” he said.

Better air quality in urban areas as a result of the lockdown could be another cause, Laine said, since airborne particles are known to be a risk factor for heart disease.

However not all are convinced that the pandemic had a positive impact on patients with all types of heart conditions.

Research published in the Journal of the American College of Cardiology in January found that, during the early phase of the pandemic, deaths due to ischaemic heart disease and hypertensive diseases increased in some parts of the US. Some patients may have died as a result of avoiding hospital visits due to infection fears, the researchers noted. 

A temporary or permanent effect?

With Finland, however,Dr Laine believes that was not the case.

“We haven’t seen any increase in mortality in cardiac diseases and so currently we think that it’s a true decrease in the number of cases and not because patients are not seeking help,” he said. “People were not dying at home to myocardial infarction”.

According to Dr Laine, the number of heart attack patients in Finland remains about 5 per cent lower than average, despite the easing of COVID restrictions.

“I think this is a typical example that environmental factors can have profound effects on myocardial infarction. And I think it’s motivating us to change our lifestyle healthier,” Dr Laine said.

Source: EuroNews

Millions of J&J Vaccines for South Africa Unfit for Use

In yet another blow to South Africa’s flagging vaccination programme, millions of the Johnson & Johnson vaccine doses meant to be used have been declared unfit for use. This is due to contamination concerns at one of the group’s facilities in the US.

The US Food and Drug Administration said that the doses were not suitable for use. Upon reviewing this decision, the South African Health Products Regulatory Authority (SAHPRA) said in a statement that it had decided “not to release vaccine produced using the drug substance batches that were not suitable”.

J&J’s Emergent plant was ordered to pause production in April several weeks after it was determined that batches of a substance used to produce the vaccine were cross-contaminated with ingredients from another jab made by Anglo-Swedish pharma giant AstraZeneca. The FDA is yet to allow the factory to reopen.

Acknowledging the setback in South Africa’s vaccination programme, acting Health Minister Mmamoloko Kubayi-Ngubane said Saturday that the batches concerned were stored in a high-security laboratory in Port Elizabeth belonging to drugmaker Aspen. Aspen meanwhile promised that it is ramping up production elsewhere to meet the shortfall, and President Ramaphosa said that he discussed with President Biden the possibility of receiving US vaccine donations.

Along with other countries South Africa, is pushing for a patent waiver on COVID vaccines to allow low cost production of generics.

“If we are to save lives and end the pandemic, we need to expand and diversify manufacturing and get medical products to treat, combat and prevent the pandemic to as many people as quickly as possible,” President Cyril Ramaphosa told the G7 group of wealthy nations meeting in Britain on Sunday. The country needs 31 million doses of the J&J vaccine to help vaccinate its population of 59 million.

South Africa has secured 30 million doses of the highly effective Pfizer-BioNTech vaccine, but is a two-dose vaccine which has significant cold chain requirements.

Emergency shipment

SAHPRA stated that there is a new delivery of approximately 300 000 J&J doses “that have been cleared by the US FDA that meet the requirements and will subsequently be released and shipped to South Africa.” The expiry date of these doses have been extended, and will be ready for administration to South African teachers within days.

Vaccinations were already paused in April after reports of rare cases of blood clots. And in February, South Africa rejected over 1.5 million doses of AstraZeneca’s vaccine as it was deemed ineffective. The J&J vaccines were already facing expiry as they had been removed from long term storage.

South Africa has only vaccinated just over 1% of its population but as far as can be ascertained with limited testing in Africa is the hardest hit by COVID on the continent, with over 1.7 million recorded cases.
Source: Eyewitness News

Children Struggle to Recognise Expressions of People with Facemasks

Image by pedro_wroclaw from Pixabay

sA new study has shown that children between the ages of 3 and 5 have difficulty in recognising the emotions of people wearing surgical masks. This collateral effect from this  measure to prevent COVID transmission could influence the correct development of children’s capabilities of social interaction.

To provide guidance for decision-makers, the World Health Organization (WHO) and UNICEF compiled a document discouraging exposure to the use of facemasks when dealing with children aged up to five years old. In addition, even for older children, WHO recommends weighing up the benefits of wearing facemasks in against potential negative impacts that could include social and psychological problems, and difficulties in communication and learning.

To investigate such possible negative impacts, a study was carried out by the U-Vip (Unit for Visually Impaired People) research team led by Monica Gori at the IIT- Istituto Italiano di Tecnologia (Italian Institute of Technology). The findings were published in Frontiers in Psychology.

A research team led by Monica Gori at the Istituto Italiano di Tecnologia (IIT) focused on the pre-school age group, helping define the measures that can be taken to reduce the impact of the use of surgical masks amongst children. While the wearing of facemasks is not mandatory from 3 to 5 years of age, children are in any case exposed to the use of such preventive measures in various everyday social and educational contexts.

The IIT researchers prepared a quiz containing images of people with and without facemasks, and displayed them on screens to 119 individuals comprising 31 children aged between 3 and 5 years old, 49 children between 6 and 8 years old, and 39 adults between 18 and 30 years old. The participants, independently or with parental assistance in the case of the youngest participants, were asked to try to recognise the faces’ expressions, with and without facemask, conveying different emotions such as happiness, sadness, fear and anger.

When those faces were covered with a facemask, the 3-5 years olds only managed to recognise facial expressions conveying happiness and sadness 40% of the time. The percentages were higher for other age groups: 6-8 years olds had a 55-65% success rate, and 70-80% adults. Generally, however, all age groups displayed some difficulty in interpreting these emotions expressed while the face was partially covered by a facemask. There were better results with other expressions, but the pre-school age children still had the greatest difficulty.

“The experiment was performed in the earliest phases of the 2020 pandemic, and at that time facemasks were still a new experience for everyone,” said Monica Gori. “Children’s brains are highly flexible, and at the moment we are performing tests to ascertain whether children’s understanding of emotions has increased or not.”

“In the study, we worked with children and adults with no forms of disability”, explained Maria Bianca Amadeo, IIT researcher, “of course, these observations are even more important when considering children affected by disabilities.” 
“Indeed”, added co-author Lucia Schiatti, IIT researcher, “for example visual impairment implies difficulties in social interaction. For such individuals in particular, it will be even more necessary to concentrate on possible preventive measures or specific rehabilitation activities”.

Further research is needed over the next few years to assess the actual impact of this mask wearing on the ability of children with and without disabilities to interact. In the meantime, the findings suggest the use of transparent facemasks for all operators in contact with children in the 3-5 year-old age group, or developing training activities to teach children how to recognise emotions by looking at the eyes.

Source: News-Medical.Net

Journal information: Gori, M., et al. (2021) Masking Emotions: Face Masks Impair How We Read Emotions. Frontiers in Psychology. doi.org/10.3389/fpsyg.2021.669432.

Urgent Vaccine Call as COVID Closes Free State Schools

Photo by Mary Taylor from Pexels


As COVID cases and deaths continue to rise in the Free State, with schools being closed, it is unclear when the province’s teachers will receive their vaccinations.

The deaths of six learners, 75 teachers, and three support staff from COVID have been reported in the Free State since March 2020.

While teachers await their vaccines, COVID still claims lives in the school system – and not just older teachers and staff. Quincy Tsoenyane lost a daughter to COVID-related complications, 18 year-old Nomthandazo Ngcoyi, who was a learner at Lephola Secondary school in Welkom. Nomthandazo was one of 11 learners at the school who tested positive for COVID in May. Tsoenyane, who is a father to two surviving children, said it pains him to know that his daughter got sick at school.

According to the Department of Basic Education (DBE), Nomthandazo developed a cough at school and was tested for COVID along with other learners. On 19 May, she tested positive and was sent home to self-isolate. She died at home six days later.

A rare case

Dr Cloete van Vuuren, an Infectious Disease Specialist in the Department of Internal Medicine at the University of Free State, said that Nomthandazo’s death is a rare case as it is uncommon for young people to die from the SARS-CoV-2 virus.

The DBE figures show that since March 2020, the Free State has recorded a total of 2101 positive cases among teachers in schools: 1377 among learners, and 461 among non-teaching staff. Outbreaks of COVID cases have forced several shutdowns of Free State schools.

Holding out for vaccines

As COVID numbers climb in Free State schools, teaching federations and unions are urging that teachers be vaccinated as soon as possible.

From 26 July, children from Grades R to 7 will return to in-person classes. In a media statement, the National Professional Teachers Organisation of South Africa (Naptosa) said that they are pleased to hear that the education sector will receive 500 000 doses of the Johnson & Johnson vaccine.

However, the union said they are still in limbo because the doses must still require verification by the Food and Drug Administration (FDA) and will expire on 28 July.

As of Thursday, there were 591 new COVID cases in Free State, with a new case incidence rate of 17.8 per 100 000 people.

Teachers need to protect themselves and others

Dr Kerrin Begg, Public Health Specialist in the Faculty of Health Sciences at the University of Cape Town reminded teachers that although it is understandable for them to be anxious about the vaccination, each and every person has the responsibility to educate themselves.

“Teachers need to be teaching themselves about the virus just like they do in their everyday line of work of teaching children.

“At the Colleges of Medicine of South Africa, we have produced school guidelines on measures to take to reduce the transmission of COVID in the school environment,” she said. She said that socialising outside of class was where most of the transmission took place, and that learners now no longer adhered to social distancing.

“We remind parents and teachers to remember that protecting themselves is not to be practiced during school hours only, but there are three major focal points of transmission which are before, during, and after school hours.

“Teachers need to understand that the environment of the classroom is very important. Fresh air is better than artificial air, outside is better than inside. Schools also need to continue to promote personal and physical distancing, and hygiene measures daily,” Dr Begg said.

Source: Spotlight

Normal Breathing Can Transport Viruses Over 2 Metres

Researchers have demonstrated that normal breathing can transport viruses in saliva droplets up a distance of up to 2.2 metres in 90 seconds.

The World Health Organization and the Centers for Disease Control recommend social distancing to prevent the spread of COVID. The distances are estimated from various studies, but there is a need for further research into how viruses are transported from one person to another. 
Previous studies considered aerosol transport after coughing or sneezing, while this study focused on normal human breathing, using computer simulations with a more realistic model than prior studies. A normal breath produces periodic jet flows that contain saliva droplets, but those jets’ velocity is less than a tenth that of a cough or sneeze.

Wearing a face mask greatly reduces the distance which these droplets can travel. Saliva droplets restricted by a mask had travelled only 0.72 metres after two minutes, far short of the distance of 1.8 metres suggested by the CDC.

The investigators found even normal breathing produces a complex field of vortices that can move saliva droplets away from the person’s mouth. The role of these vortices has not previously been understood.

Study author, Ali Khosronejad, American Institute of Physics said: “Our results show that normal breathing without a facial mask generates periodic trailing jets and leading circular vortex rings that propagate forward and interact with the vortical flow structures produced in prior breathing cycles.”

This complex vorticity field can enable the transport of aerosol droplets over long distances despite the slow speeds. A face mask serves to dissipate the kinetic energy of the jet produced by an exhaled breath, thereby disrupting the vortices and limiting the travel of virus-laden droplets.

The researchers also took into account evaporation of the saliva droplets. With no mask, they found the saliva droplets near the front of the plume of exhaled breath had partially evaporated, reaching a size of only one-tenth of a micrometre. In stagnant indoor air, it would take days for droplets this small to settle to the ground.

Masks partially redirect the exhaled breath downward, significantly restricting forward motion of the plume, so the risk of suspended droplets remaining in the air is substantially reduced.

“To simplify the breathing process, we did not consider the flow of air-saliva mixture through the nose and solely accounted for the flow through the mouth,” Khosronejad said. “In future studies, we will explore the effect of normal breathing via both the nose and mouth.”

Source: News-Medical.Net

Journal reference: Khosronejad, A., et al. (2021) A computational study of expiratory particle transport and vortex dynamics during breathing with and without face masks. Physics of Fluids. doi.org/10.1063/5.0054204.

ImmunityBio Vaccine Trial Expanding in Western Cape

In addition to traditional subcutaneous administration for the vaccine candidate, the trial will measure immune responses generated by sublingual and nasal administration routes. Photo by Gustavo Fring from Pexels

The Phase I clinical trial of ImmunityBio’s experimental COVID vaccine, designed to be effective against COVID variants, is about to be expanded to include different administration routes as well as effectiveness in people who previously had COVID. 

Co-investigator Prof Graeme Meintjes, second chair in the Department of Medicine at UCT, said that the Phase I trial has started and is still ongoing at the Wellcome Centre for Infectious Diseases Research in Africa’s (CIDRI-Africa) Khayelitsha clinical research site.

He said that the first two cohorts of ten participants each both received two subcutaneous injections of the vaccine, three weeks apart, with one cohort receiving a higher dose.

“The purpose of that was to assess safety, so participants were followed up very carefully for side effects and for reactions to the vaccine. And the review of that suggests no major safety concerns,” he explained. He added that the Phase I trial design has since been adapted to include four more cohorts, which is going through the approval process.
These four additional cohorts will include people who have had COVID because the researchers want to look at the effect the vaccine will have on boosting existing immunity against COVID. Each cohort will have ten participants, bringing the expected total number of participants for Phase I to 60 people.

New administration routes

To see whether different administration routes produce a sufficient immune response, each participant in these new cohorts will receive one dose of the vaccine through one of four routes. These would be either a subcutaneous injection, a sublingual route, a combination of subcutaneous injection and sublingual method, or an intranasal route.

“We’ll be measuring the antibody responses as well as the T-cell responses to the vaccine, but we do not have results yet,” said Meintjes. He added that enrolment should be complete in the next two months, pending the outcome of the approval process.

Phase II/III trial plans

Phase II and Phase III trials in South Africa are being planned, which will be headed by the South African Medical Research Council (SAMRC), Mentjes confirmed.

Details will be made available once the trial has been approved by SAHPRA. It is unlikely that placebos will be used, now that vaccines are shown to be effective; rather different vaccines will be compared.

Broader immune response with two-pronged defence

The vaccine has been designed to potentially offer a broader, long-lasting immune response, Mentjes noted. In this way it should also provide improved protection against COVID variants.

Currently, most of the COVID vaccines are designed to produce an immune response against the spike protein of the virus, but it mutates rapidly, allowing certain variants to partially or fully escape vaccines. 

The ImmunityBio vaccine aims to offer a two-pronged or dual defence, Meintjes said, with the vaccine containing two proteins from the SARS-CoV-2 virus: the spike protein along with the more stable nucleocapsid protein. The nucleocapsid is an RNA-binding protein which is critical for viral replication and genome packaging.

He explains that targeting nucleocapsid could potentially provide more durable and long-term protection against different variants of the SARS-CoV-2 virus because the immune system will recognise the nucleocapsid even when the spike protein changes.

“The hope is that by including the nucleocapsid you would generate a vaccine response that covers emerging variants, those that have emerged and those that might emerge in the future,” he says.

Human-adenovirus based vaccine carrier

The ImmunityBio vaccine will use an adenovirus vector to deliver the antigens. Director of the Africa Health Research Institute (AHRI), Professor Willem Hanekom, explained that a vector is needed in order to stimulate the immune system’s response, and a viral vector is effective since it is foreign to the immune system, helping provoke an immune response. The virus is designed to simply carry the antigens into the body.

The AstraZeneca vaccine uses a modified chimpanzee adenovirus while Johnson & Johnson’s uses the human adenovirus Ad26, which has been used before in a number of vaccines including HIV. ImmunityBio’s vaccine uses the human adenovirus hAd5, which was initially used in failed gene therapy trials — but which proved to be an excellent vaccine delivery system. However, its development over the past two decades has been halting.

According to Prof Hanekom, if there is previous immunity against the adenovirus being used in a vaccine, the immune system will destroy it before the antigens inside are released. This has been circumvented with the ImmunityBio vaccine so that the immune system doesn’t immediately recognise the hAd5 vector. There was concern that the Johnson & Johnson vaccine would have limited efficacy in sub-Saharan Africa due to the fact that about half the population have immunity to Ad26.

“They’ve modified the adenovirus so it will still work and still be seen by the immune system even if there is pre-existing immunity because they’ve taken out the parts that the pre-existing immunity sees,” Prof Hanekom said.

Enhanced T-cell response

The vaccine is specifically designed to elicit strong T-cell responses to the nucleocapsid, and this has been seen in animal studies, Mentjes noted.

“Obviously one purpose of these studies is to see whether this design element generates those strong T-cell responses in humans as well,” he says. “All COVID vaccines elicit T and B cell responses, it’s not one or the other. But this (vaccine) is specifically designed to enhance those T-cell responses.”

B-cells and T-cells form part of the body’s adaptive immune response. B-cells form the antibodies to respond to a pathogen, and when the virus is introduced again, memory B-cells provide the antibodies to respond quickly.

Vardas says that with the ImmunityBio vaccine, B-cells and memory B-Cells will be formed that will remember the spike protein and the nucleocapsid and how to attack it. She likens this to a sniper attack. She explains that when a memory B-cell detects the spike or nucleocapsid protein, it signals for the production of B-cell antibodies. These antibodies then coat the outside of the virus, which signals the T-cells to attack and essentially “eat up” the virus-infected cells.

There are two types of T-cells, explains Vardas – CD4 cells which attack the virus, and CD8 cells, which also form a memory cell as the B-cell does. “You’ll have groups of CD4 and CD8 cells that are spike protein-specific and groups that are nucleocapsid specific, so improving that kind of attack to two sides of the war,” said Vardas.

Source: University of Cape Town