The advent of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) pandemic and the dynamics of its spread is unprecedented. It is therefore, of paramount importance to get a vaccine that can stop the spread of the virus.
But basic knowledge about the virus and kinetics of immune responses against it is still emerging. An added difficulty is that different strains of SARS-COV-2 have been reported – even in the same country – within six months of its emergence.
Vaccines are preventive or therapeutic interventions that dramatically reduce morbidity and mortality caused by infectious diseases. They are clinically simple but immunologically complex. Edward Jenner is considered to be the father of vaccinology because he developed the first vaccine to prevent smallpox over 200 years ago. This led to the global eradication of the disease and the development of more life vaccines.
Over the intervening two centuries vaccinology has developed into a multidisciplinary intervention. It involves scientists from fields such as microbiology, immunology, medicine, epidemiology, statistics, policy, manufacturing, molecular biology, public health and even ethics.
All these disciplines are being deployed in the search for a vaccine against SARS-CoV-2.
An arduous process
Generally, good vaccines have three essential features.
First, they must be safe to administer.
Second, they must produce the appropriate type of immunity (antibody and/or cell-mediated) for the disease in question.
Third, they must be inexpensive for the target population and they must take into account geographical, gender and age differences.
To achieve these features, vaccine development undergoes a sequence of carefully implemented ethical processes and procedures. These are staged into pre-clinical and clinical development – with four developmental phases which usually span a number of decades. This is because there’s a need to understand the mechanisms of protection against the pathogen, and to mitigate the potential risk of vaccine-induced adverse reactions.
This takes time. And variations almost invariably emerge.
For example, geographical variation was reported in the efficacy of the rotavirus vaccine. In Malawi and South Africa its efficacy was found to be between 49 and 77 percent. But in developed countries it was 95-96 percent. A recently completed study in our laboratory showed that the roundworm, Ascaris, affected the efficacy of oral rotavirus and poliovirus vaccines.
Similarly, geographic or other variations could be encountered in the development of a vaccine for Covid-19 given that cardiovascular diseases, asthma, diabetes and ageing have been reported to aggravate the infection.
Hurdles to clear
Immunologically, every antigen, including vaccine, is processed by the first line of defence, the innate immune system, and if need be passed on to the adaptive immune system.
These two lines of defence are tightly linked and finely controlled to attack different antigens in different ways. The aim is to eliminate the antigens while avoiding unintended damage to the healthy parts of the body.
Vaccine effectiveness is solely dependent on the adaptive arm of immune response. In this arm, specialised cells including the B cells and T cells are the major players. They have precise specificity for germs and provide long-term protection.
When a kind of blood cell, B lymphocyte, is in contact with foreign particles it multiplies to produce many plasma cells. These secrete antibodies whose major function is neutralisation of pathogens. In the development of a Covid-19 vaccine, researchers must identify a small part of coronavirus that will elicit effective neutralising responses.
Antivirus vaccines that lead to production of non-neutralising antibodies can facilitate deposition of complexes in tissues and activate several pathways that can worsen pathologies associated with the viral infection or excessive production of inflammatory cytokines as reported in some patients with severe Covid-19. This clearly indicates that when a protective immune response is compromised, massive damage to vital organs such as the lung, liver and the kidney can occur. Thus, damaging immune responses should be avoided by any Covid-19 vaccine.
Another blood immune cell in vaccine efficacy is the T lymphocytes. For effective Covid-19 vaccine, careful activation of certain types of T cells and monitoring of their pattern of responses are essential. For example, two types of T-lymphocytes (CD8+ T cells and CD4+ Th-1 responses) are required for the removal of SARS-CoV-2. But CD4+ Th-2 responses are not responsible for the elimination of SAR-CoV-2. It is well known that accentuation of Th-2 responses supports eosinophil recruitment, airway hyper-responsiveness, mucus production, and can weaken cytolytic T cell activity to cause delayed viral clearance and airway dysfunction. This type of unwanted response has been reported after vaccination against respiratory syncytial virus infection.
No cutting corners
The pressure to develop a Covid-19 vaccine is huge. But its development without fully understanding the kinetics of immune responses involved in the disease and the safety risks of the vaccine could bring unwarranted setbacks – now and in the future.
In addition, SARS-CoV-2 might mutate in ways that would make previously effective vaccines useless.
A great many steps have to be taken in the development of any vaccine. With Covid-19, there are added complexities given that its severity appears be different across gender and age. There’s also evidence that it might be mutable and that it has different strains. Then there’s the fact that it’s very new, which means there’s still limited knowledge about immune responses to SARS-CoV-2.
In addition, a multiplicity of disciplines must be involved. A safe and effective vaccine won’t be developed without detailed understanding of host-pathogen interaction. This is happening in the trials that are being currently run.
What this adds up to is that a safe and efficient Covid-19 vaccine might not be realised soon.