Is 'original antigenic sin' complicating indian vaccination drive against Covid-19?

India is in the grip of a devastating second wave of Covid-19. Many experts believe new variants of concern (VOC) are behind this unprecedented surge. Some media reports are hinting toward higher risk of Covid infection following Covid vaccinations. 'Original antigenic sin,' in which a prior exposure to an antigen leads to an ineffective response to a related antigen, may offer one immunological explanation for this unusual association. There is an urgent need of undertaking a detailed study to prove/disprove this association.

Emergency use authorisation of Covid-19 vaccines: An ethical conundrum.

Large-scale vaccination with a safe and effective vaccine against Covid-19 is the only way to conquer the ongoing lethal pandemic that has led to extraordinary social and economic upheaval globally. Fortunately, the world is on the verge of developing Covid-19 vaccines in an unprecedentedly short time. More than forty vaccines are in different stages of clinical trials, and a few are in the crucial phase III studies stage. A new demand for emergency use authorisation and rapid deployment of these vaccines before scrutinising phase III trial data is raging in different quarters. Can advancement of the deployment of these vaccines by even a few weeks give us rich public health dividends? Would it be ethical to deploy these novel vaccines based only on the safety and immunogenicity data generated by the phase-I and II clinical trials? Would it be ethical to deny vaccination of vulnerable populations against an untreatable infectious disease despite the availability of reasonably safe and efficacious vaccines for the want of phase III trial data? The answer is not straightforward, as there are many complexities involved. This commentary attempts to discuss some ethical issues involved in a decision to deploy Covid-19 vaccination before phase III trial results are declared.

Are BCG-induced non-specific effects adequate to provide protection against COVID-19?

The world is experiencing a pandemic of Coronavirus Disease (COVID-19) caused by type-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Vaccination is the only option to prevent future surges of the disease. Efforts for developing an effective vaccine are underway, but the timeline for the widespread availability of safe and effective vaccines is unknown. Some ecological reports have linked regional universal use of the Bacillus Calmette-Guerin (BCG) vaccine with reduced morbidity and mortality of COVID-19. BCG protects from non-tuberculous diseases through 'non-specific' effects mediated by the modulation of innate immunity. This commentary provides details of the immunological mechanism of BCG-induced 'trained innate immunity' responsible for its nonspecific protective effects. A probable role of the BCG vaccine in the current pandemic is also examined.

Development of SARS-CoV-2 vaccines: challenges, risks, and the way forward.

The COVID-19 pandemic mandates the development of a safe and effective Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccine. This review analyzes the complexities, challenges, and other vital issues associated with the development of the SARS-CoV-2 vaccine. A brief review of the immune responses (innate, antibody, and T-cell) to SARS-CoV-2, including immune targets, correlates of protection, and duration of immunity is presented. Approaches to vaccine development including different vaccine platforms, critical attributes of novel vaccine candidates, the status of the ongoing clinical trials, and the ways to speed up vaccine development are also reviewed. Despite a historical average success rate of only 6%, and a usual gestation period of 10-12 years for the development of a new vaccine, the world is on the verge of developing COVID-19 vaccines in an extraordinary short time span.