In the informal chat that followed the panel discussion, Birx asked me about India’s ongoing vaccination programme. After hearing about the virus vector vaccine (Covishield) and the inactivated virus vaccine (Covaxin), she suggested we also produce and use sub-unit protein vaccines that are safe. She said India has a high level of expertise in their production.
Jewel in the Corona
Six months later, news emerged that two protein sub-unit Covid vaccines produced by reputed Indian manufacturers (Corbevax and Covovax) were ready for introduction into India’s vaccination program and the global supply chain.
Both statements made by Birx are true. India has a creditable record for producing and exporting protein sub-unit vaccines. Hepatitis B, Hepatitis E and Human Papilloma virus vaccines are examples. Protein sub-unit vaccines are safe, because they use only a part of the microbe as an antigenic stimulus, avoiding any possibility of disease being caused by the whole organism. Further, these vaccines have not been associated with adverse effects such as myocarditis linked to mRNA vaccines or venous and arterial thrombosis observed in some persons receiving virus vector vaccines.
Sub-unit vaccines use a fragment of the virus or bacterium that is a prominent antigen capable of evoking a good immune response, and is also usually involved in the pathogenesis of the disease. The microbial fragment may be a protein, sugar (polysaccharide) or a combination (conjugate). In the case of the Sars-Cov-2 virus, the chosen antigen is the spike protein that the microbe uses to attach itself to the human cell surface and open the door for entry into the cell.
Unlike mRNA vaccines that introduce the genetic code for in vivo manufacture of the spike protein by human cells, the recombinant protein sub-unit vaccines supply an externally produced spike protein fragment to the body. This does not involve the human genetic machinery in the production of the antigen. Because the whole virus is not used, the immune response will be selective and not directed to other antigens of the microbe.
Protein sub-unit vaccines like Corbevax are usually made by inserting the genetic code of the antigen into yeast cells, which are easy to grow and are prolific in protein production. Grown in fermentation tanks, they are split open to extract the antigen. Covovax uses an engineered baculovirus to infect cultured moth cells. Spike protein produced by them is assembled on synthetic lipid nanoparticles.
Since the antigen used in these vaccines is only a part of the microbe, it may stimulate copious antibody production, without generating cytotoxic T-cells that can kill the virus. For this reason, sub-unit protein vaccines are usually combined with an ‘adjuvant’ chemical that can mobilize T-cells. Corbevax uses the Receptor Binding Domain (RBD) of the spike protein as the antigen and an adjuvant comprising alum and CpG 1018. Covovax uses a saponin-based adjuvant.
Vax Still the Silver Bullet
Covovax was mainly produced for export, as the India-made brand of Novovax. Produced by Hyderabad based Biological Evans, Corbevax was developed in partnership with a Houston-based firm linked to scientists from Baylor College of Medicine. With waiver of intellectual property rights, this vaccine is available for production and use in developing countries.
Presently, it is approved for use in India and Botswana. It is awaiting WHO’s approval that will make it eligible for use across the world. Since many individuals have by now had earlier exposure to virus and vaccines, evidence of efficacy of Corbevax is based on the augmented immunological response to the vaccine.
In India, the Covid sub-unit vaccines were originally cleared for two-dose primary vaccination of children, due to the general track record of safety of such vaccines. With the manufacturers claiming high levels of antibody production in their studies, the sub-unit protein Covid vaccine has also recently received approval for use as a ‘heterologous’ booster in Indians who had earlier received two or three doses of Covaxin or Covishield.
Studies across the world have shown that heterologous vaccine administration, which sequentially uses vaccines made from different platforms, is more effective in providing protective immunity when compared to homologous regimens that repeat the same vaccine. Availability of a safe sub-unit protein vaccine will enable those who seek booster doses to protect themselves. Even when Omicron variants like BF.7 are exhibiting increased capacity for evading previously acquired immunity, a surge of antibodies from such boosters may be capable of preventing severe disease in those who are infected.
When and in whom such vaccines should be used in a frequently changing pandemic scenario is to be determined by evidence-informed recommendations of public health experts, judicious government policy and intelligent individual choices. However, the increase in our vaccine armoury boosts confidence that we will not be limited in our choices.