OP-ED

South Africa has the experience and capacity to make a Covid-19 vaccine

By Janusz Pawęska, Stefan Swanepoel, Christiaan Potgieter, Baptiste Dungu, Morena Makhoana, Lynn Morris 30 June 2020

A volunteer receives an injection from a medical worker during the country's first human clinical trial for a potential vaccine against Covid-19 at the Baragwanath Hospital on 28 June 2020 in Soweto. (Photo: Gallo Images / Beeld / Felix Dlangamandla)

South Africa should consider the possibility of domestic Covid-19 vaccine production using local isolates and well-established vaccine technologies, eg, production of inactivated and live-attenuated vaccines.

The ongoing Covid-19 pandemic is due to the rapid spread of a new zoonotic (animal origin) coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Over the last several decades, there has been on average almost one new emerging disease (EID) each year, of which approximately 75% have been zoonotic. The most recent epidemics of Ebola virus disease, Zika virus disease, and now Covid-19 demonstrate the global significance of EIDs and the lack of adequate capacities in their prevention, detection, diagnosis, surveillance, response and research.

Microbes, and particularly RNA viruses continue to rapidly evolve and adapt, and with the acceleration and expansion of global trade, human movement and travel and the escalating populations of both people and animals, they have an even greater opportunity to adapt, change, and be transported to new hosts and ecosystems, often with disastrous results.

It became evident that once more the world is not adequately prepared to effectively and timeously respond to a newly emerged zoonotic contagion. The health, humanitarian and socioeconomic impacts of the Covid-19 pandemic are huge and dramatic both on individual, family, community and global levels and require a major change in our minds and actions.

What are coronaviruses?

Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. The name “coronavirus” is derived from Latin corona, meaning “crown” and refers to the characteristic appearance of coronavirus particles or virions observed under electron microscopy – an image reminiscent of solar corona created by the viral surface proteins.

Coronaviruses display high genetic plasticity driven by the accumulation of point mutations and recombination events. This genetic variation is probably responsible for the emergence of viral strains with increased virulence, different tissue tropism and for expanded host range.

Of more than 30 different coronavirus species identified to date, many infect livestock (cattle, swine, poultry, horses, camels), companion animals (dogs, cats), wildlife (eg, bats, civet cats, pangolins, mice, rats, hedgehogs), cetaceans and bulbuls.

Coronaviruses are subdivided into four genera, alpha-, beta-, gamma-, and deltacoronaviruses. Many alpha- and beta-coronaviruses have their origin in bats, while gamma- and deltacoronaviruses have their origin in birds.

Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by infectious bronchitis virus. Subsequently, a number of other animal coronaviruses were described, including mouse hepatitis and transmissible gastroenteritis viruses.

Human coronavirus causing a common cold was first discovered in the 1960s. There are currently seven known human coronaviruses, four causing a common cold (229E, OC43, HKU1, NL63), and three more recently described and being highly pathogenic, namely SARS-1, MERS and SARS-CoV-2. Infections with both animal and human coronaviruses result in a range of diseases, but mostly in respiratory symptoms or/and gastroenteritis. 

How to respond to the Covid-19 global challenge

Despite drastic control measures, including prolonged lockdowns and social distancing, any significant progress in controlling and managing the Covid-19 pandemic and future prevention and treatment against infection with SARS-CoV-2 would likely be only possible when effective mass immunisation and antiviral drug treatments are available.

The successful control of the Covid-19 pandemic, and protection of people against SARS-CoV-2 infection, require a quantum leap in the development of Covid-19 vaccine candidates. Different technologies can be utilised to develop vaccines, including inactivated, modified-live, genetically modified-live, recombinant protein, DNA, mRNA, virus-like particle, virus replicon, and virus-vectored vaccines.

The current Covid-19 vaccine research and development (R&D) landscape includes more than 140 vaccine candidates, being developed and subjected to different levels of pre-clinical and clinical evaluation, mostly in North America, Asia, Australia and Europe. Traditionally, it takes on average more than 10 years to develop and license a safe and efficacious vaccine for large-scale manufacturing and massive public use. It appears, however, that the scale and speed of the global vaccine R&D effort in response to the Covid-19 pandemic, might deliver a vaccine by the end of 2020 or early 2021, which could be used under emergency regulations.

Of the more than 140 vaccine candidates under development against SARS-CoV-2 listed by the World Health Organisation, at least 13 are already at different stages of clinical trials in humans. Some promising results are already showing that protective immunity in non-human primate challenge studies can be induced using an inactivated whole SARS-CoV-2 vaccine and adenovirus-vectored vaccine, encoding the spike protein of SARS-CoV-2. 

Need for inter-sectoral One Health effort to deliver vaccine

The Covid-19 pandemic calls for well-coordinated and cooperative measures through sharing experience, knowledge, and efforts by public and veterinary health professionals, including governmental, academic and private institutions. An inter-sectoral One Health network is highly pertinent in response to the Covid-19 pandemic and lessons learned from veterinary coronavirus vaccines should be applied to the development of Covid-19 vaccines. 

What can be learned about Covid-19 vaccination from veterinary coronavirus vaccines?

A number of commercial inactivated and live-attenuated veterinary coronavirus vaccines have been successfully developed to prevent coronavirus infections in domestic and companion animals, including:

  • Inactivated vaccine against bovine coronavirus (BCoV) associated with neonatal calf diarrhoea and newborn calves. Immunisation of pregnant cows and heifers induces protective virus-neutralising antibodies which upon transfer via colostrum (passive immunity) reduce disease in calves. The inactivated BCoV vaccine antigen is generally formulated in a combination multivalent vaccine, including other vaccine antigens associated with neonatal calf diarrhoea.
  • Inactivated feline enteric coronavirus (FECV) against antigenically similar canine coronavirus (CCV) causing a sudden onset of vomiting, depression, loss of appetite, diarrhoea, and in a small proportion, deaths in young puppies. This vaccine can be formulated in combination with other canine pathogens including attenuated distemper virus, adenovirus, parvovirus and parainfluenza virus, and inactivated leptospirosis antigens.
  • Live-attenuated vaccine against transmissible gastroenteritis virus of swine (TGEV) causing a fatal disease in young pigs characterised by acute diarrhoea, vomiting, dehydration and sudden death. This vaccine given to pregnant sows provides passive immunity in piglets.
  • Live-attenuated vaccines against avian infectious bronchitis virus (IBV) causing an acute respiratory disease and reduction in both the quantity and quality of egg production. These vaccines can be used in breeders and layers to prevent egg production losses, as well as to pass protective maternal antibodies to progeny.

The long-standing experience and knowledge in the development and production of veterinary coronavirus vaccines should be utilised to benefit and speed the development and manufacturing SARS-CoV-2 human vaccine.

Mobilisation of local resources in response to emergence of epidemic-prone zoonotic pathogens

Ability and willingness to mobilise and optimise South Africa’s fight against Covid-19 could serve as a model for triggering domestic transformation of R&D capacity in response to the emergence and re-emergence of epidemic-prone zoonotic pathogens. The Covid-19 crisis prompted a global response and demonstrates that there is willingness to address formidable encounters with global approaches and strategic partnerships; however, a national response is pivotal to safeguard the health, socioeconomic and social well-being of South Africans.

While there is a promise from global leaders that at least the initial immunisation of human populations worldwide will be free of charge and accessible to all, establishment of potential endemicity of SARS-CoV-2 both in human and animal populations (including reverse zoonoses to wildlife) constitutes a long-term contest.

Covid-19 is a reminder that even if vaccines were to be made in abundance and be made available free, unless domestic R&D and production capability are supported and enhanced, South Africa and Africa will remain a net consumer and be continuously dependent on external supplies and may not be able to respond to future pandemics. Consequently, one should consider the possibility of domestic Covid-19 vaccine production using local isolates and well-established vaccine technologies, eg, production of inactivated and live-attenuated vaccines.

Traditional inactivated viral vaccines that are relatively simple and easy to produce remain the most widely used for combating diseases such as polio, influenza, rabies, hepatitis A, yellow fever, rabies, and pertussis. At least four inactivated vaccines for Covid-19 are under development by manufacturers in China and preliminary results in humans indicate they are safe and induce good immune responses.

Can we produce an inactivated Covid-19 vaccine here?

Immunisation is one of the greatest medical achievements in human history, and has saved millions of lives. South Africa has a longstanding experience in the development of vaccines, including inactivated vaccine for poliomyelitis produced in the 1960s by the Poliomyelitis Research Foundation.

South African vaccine and biotechnology companies specialising in veterinary and public health have well-developed manufacturing capabilities, including quality-assured culture media production, virus propagation in cell culture,  inactivation, formulation and freeze-drying procedures, pilot and large-scale vaccine manufacturing, labelling and packaging, quality control of vaccine products as well as warehouses with significant cold-storage capacity. These capabilities also include the capacity to develop and manufacture animal coronavirus vaccines, and both live and inactivated vaccines against other zoonotic pathogens under certified practices.

A One Health approach has great potential to accelerate and catalyse capacities in building a Covid-19 vaccine R&D platform. This platform would not only serve to respond to the current Covid-19 pandemic but also to future virus-causing pandemics.

Pooling available human and technical resources, knowledge and expertise through an alliance of local private vaccine/biotechnology companies and public health institutions has a great potential to achieve this goal. DM/MC

Prof Janusz Paweska is the head of the Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases (NICD). Dr Stefan Swanepoel is general manager at Deltamune, which is involved in the development and production of animal vaccines; Dr Christiaan Potgieter is molecular virologist at Deltamune; Dr Baptiste Dungu is the CEO, Onderstepoort Biological Products; Dr Morena Makhoana is the CEO of Biovac which is involved in the development and production of human vaccines; Prof Lynn Morris is the interim director of the NICD and involved in HIV vaccine development.

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