Vaccine efficacy: What's holding India back from ramping up genome sequencing

No sooner was the novel coronavirus identified, its genome was sequenced and monitored closely at a global level for mutations.

Genome or gene sequencing is an advanced method by which researchers ascertain the genetic information patterns of an organism.

It also provides insights into the likelihood of changes or mutations in the genes as part of the organism’s natural survival mechanism. Knowledge of these changes helps in designing and developing therapeutics.

With new variants of coronavirus such as the UK, South Africa, and Brazil strains threatening to affect vast populations, there is a greater necessity to quickly identify newer and dangerous mutations.

As vaccines are being rolled out across the world, and there are apprehensions regarding their effectiveness, genome sequencing would provide valuable inputs to tweak vaccine design, thereby improving their range and efficacy.

Presently, countries like the UK and USA have formed consortiums (UK-COG and SPHERES), cataloguing the viral genome database comprehensively.

In contrast, India has done little compared to its maximum capacity, contributing only a few thousand samples to the database, despite the rampant COVID-19 cases.

Dr Rakesh Kumar Mishra, director, CSIR-Centre for Cellular & Molecular Biology (CCMB), Hyderabad, and Dr Amit Dutt, principal investigator at Advanced Centre for Treatment Research & Education in Cancer (ACTREC), Navi Mumbai—who had presented their analysis of the Indian SARS-CoV-2 genomic database recently—explain the issues behind genome sequencing in India.

1.    Why are there only a few thousand SARS-CoV-2 gene sequences in the Indian database? Do we lack the infrastructure?

The pandemic caught the world unawares. Both the experts opine that in India, sequencing was not the national priority. The focus was on detecting and managing the outbreak.

“Despite this, a few thousand viral isolates were sequenced at various centres, though not extensively,” says Dr Mishra.

Also, the researchers say that India has an adequate genome sequencing infrastructure for such needs. However, what was lacking was a national-level strategy and integrating the data across different populations and regions.

Dr Dutt adds, “India imports sequencing reagents which have a short shelf-life and cannot be stored in bulk. The world-wide lockdowns disrupted the supply. Institutions were constrained by short supply and funds, and hence could not prioritise sequencing.”

2.    How are we disadvantaged because of this? How can genome sequencing help assess the present situation?

As the number of cases started to decline, it further diverted the attention from sequencing. Unlike in some countries, no highly infectious dominant mutant surfaced in India. The few thousand samples sequenced so far have emerged from the collaborative work of a few CSIR, DBT, DAE and ICMR institutes.

However, one cannot be too sure that nothing is around the corner, say the experts. They are again unanimous in expressing that with new variants originating and circulating from the UK, Brazil, and South Africa, the importance of a comprehensive genome sequencing effort and database is pertinent.

Having adequate sequencing strategies is necessary to catch the variants before they begin circulating beyond control, necessitating a rigorous sequencing protocol.

Dr Dutt opines that although the repercussions so far are minimal, going ahead, there can be a heavy toll if sequencing is not prioritised. “If the steadily mutating virus evolves to acquire features like immune evasion and higher transmissibility, it can impact the vaccine efficacy,” he says.

Dr Mishra adds that, so far, these variants are mostly linked to travel history with no lateral transmissions—either due to effective containing measures or the variant is not as infectious for our population.

“However, a close watch on such variants and also potential new ones are required,” he says.

3.    What could be the remedial measures to fast-track the sequencing process? Are there funding impediments?

“There should be adequate funds to ramp up the SARS-CoV-2 genome database, which is likely to be available soon,” says Dr Mishra.

Dr Dutt, however, feels that “cash endowments for the institutes instead of sanctions for funds can help hasten the process.”

The two researchers feel that the hurdles lie in a unified sample collection strategy from across the country and the networking between each state, region, and sample collection centres.

“An effective strategy, as assessed by government think-tanks, would be to mandate that at least 5% of new positive COVID-19 cases from across different geographical regions must be sequenced,” says Dr Mishra.

Dr Dutt urges that the sequencing data must be made readily accessible to the research community: especially to genomic and computational experts, evolutionary biologists, statisticians and epidemiologists.

“Adopting automated computational tools to analyse the genomic data can save time,” he says. To this end, he suggests that an open-source computational tool developed by their group called the Infectious Pathogen Detector can be useful. (Their study is published in a peer-reviewed journal Briefings in Bioinformatics).

Both experts opine that rapid collection and transportation of samples, quick extraction and processing of the genome, and maintaining quality checks at various levels will be the critical factors for governing sequencing protocols’ efficacy.

4.    Comments on INSACOG

In the wake of the newly emerging dominant SARS-CoV-2 variants, the government formed the Indian SARS-CoV-2 Genomics Consortium (INSACOG) in December 2020.

INSACOG aims to accelerate virus surveillance, genome sequencing and characterisation.

“INSACOG is a very comprehensive and useful initiative, on par with other consortiums abroad,” says Dr Mishra.

Dr Dutt agrees, “It’s a very promising, timely and welcome initiative.”

Dr Mishra points out that INSACOG needs to integrate state government bodies, which adequately connect the regional sequencing centres so that the samples reach the sequencing centres in time and in good condition. After which, the sequenced data can be transferred electronically to the database.

“I trust that in a week or so, various strategies will roll out under INSACOG,” he concludes.