1.Cuba develops the world’s first conjugate vaccine for COVID-19

The design and manufacturing of the conjugate vaccines allows them to be stored in regular refrigeration settings of 2–8 degree Celsius

Cuba’s State-run corporation, BioFarma, said on Friday that its indigenously produced Soberana 2 vaccine was 91.2% efficacious in phase-3 trials. This follows closely on an announcement that another of its vaccines, Abdala, had reported an efficacy of 92.8% in late stage trials.

The greater-than-90% efficacy puts them in a select league; however, unlike the Pfizer-BioNTech and Moderna vaccines that had reported an efficacy of over 90%, both the Soberana and Abdala are three-shot vaccines.

Both are subunit vaccines, meaning that a part of the virus fiorms the antigen and s hitched on to another construct. In Abdala the spike protein of the coronavirus is combined with a chemically manufactured adjuvant, whereas in Soberana 2, the spike protein is chemically linked to the tetanus toxoid, making it a conjugate vaccine. The design and manufacturing allows the vaccine to be stored in regular refrigeration settings of 2–8 degree Celsius.

Conjugate vaccines

The most common conjugate vaccines are those used for Haemophilus influenza type b and the pneumococcal bacteria. However, a unique aspect of the Soberana vaccine is that it is by far the only one among coronavirus vaccine candidates that relies on the conjugate vaccine technology.

Marlene Ramirez Gonzales, one of the scientists involved in the Cuban vaccine development project, in a March letter to the British Medical Journal explained the rationale:

“The [Carribean] island’s four vaccine candidates against COVID-19 are developed as subunit vaccines, one of the most economical approaches and the type for which Cuba has the greatest know-how and infrastructure. From protein S – the antigen or part of the SARS-CoV2 virus that all COVID vaccines target because it induces the strongest immune response in humans – Cuban [vaccine] candidates are based only on the part that is involved in contact with the cell’s receptor: the RBD (receptor-binding domain) which is also the one that induces the greatest number of neutralising antibodies…Cuba had already developed another vaccine with this principle. It is Cheimi-Hib, ‘the first of its kind to be approved in Latin America and the second in the world’, against haemophilus influenzae type b, coccobacilli responsible for diseases such as meningitis, pneumonia and epiglottitis.”

Experts say that while there are no inherent disadvantages to taking a conjugate-vaccine approach for coronavirus vaccines, they have generally been used against bacteria and not viruses.

The two parts of a conjugate vaccine are typically connected by chains of polysaccharides, according to epidemiologist and public health expert, Chandrakant Lahariya, and they generally induce a weaker immune response in young children. “Cuba has a long history of vaccine development and has developed certain platforms that work to their advantage. So it makes sense for them to adopt this route. There is nothing inherently disadvantageous, though, to this approach,” he said.

Effective response

For an effective vaccine response, not only antibodies but even killer T-cells, or those produced by the immune system and capable of destroying infected cells, must be produced. In a protein sub-unit vaccine, the spike protein may be able to elicit a strong antibody response but when combined with the tetanus toxoid, a very widely used childhood vaccine and therefore one which the immune system recognises, such a T-cell response could also be generated and conferring more effective protection, said Shahid Jameel, virologist and Director, Trivedi School of Biosciences, Ashoka University.

He added that while there could be “logistic” concerns with a three-dose vaccine, it wasn’t right to compare efficacies of various vaccines as those numbers had different contexts. “Every vaccine’s efficacy results are in comparison to placebo, and not against another vaccine…. each trial was done differently.”

While the efficacy results of the Cuban vaccines haven’t been published in peer-reviewed journals, that the vaccines have been developed entirely by the public health system and amidst a U.S. trade embargo, are among the reasons why they have evoked interest in several other Caribbean countries as well as beyond.

Global response

Iran’s Pasteur Institute has said it will participate in phase-3 clinical trials for Soberana 02, with another 60,000 to be enrolled in Venezuela. Other countries including Mexico, Jamaica, Vietnam, Pakistan and India have expressed an interest in the Cuban vaccines, as has the African Union (on behalf of all 55 of the African nations). Cuba, which exports medical services, has said it will apply different rates for vaccines depending on the importer’s ability to pay.

2.The 2020 Millennium Technology Prize goes to…

Balasubramanian and Klenerman for DNA sequencing techniques

The 2020 Millennium Technology Prize, announced in May, has been awarded to Shankar Balasubramanian and David Klenerman, “for their development of revolutionary DNA sequencing techniques.” Their work is a perfect blend of science and innovation, and very apt as we have all heard a great deal about genome sequencing in the context of the ongoing pandemic.

Emphasis on innovation

Awarded by the Republic of Finland, along with top Finnish academic institutions and industries, The Millennium Prize has a 21st century outlook, with a strong emphasis on innovation. Past winners include Tim Berners-Lee (for implementing the world-wide web) and Frances Arnold (for her work on directed evolution in a laboratory setting). Three of the eleven awardees so far have subsequently won Nobel prizes. We wait, with bated breath, for Balasubramanian and Klenerman!

Shankar Balasubramanian was born in Chennai, and has lived in England for most of his life. After his PhD, he joined the Chemistry Department, Cambridge University. He teamed up with David Klenerman, recruited by the Department around the same time. The initial aim was to build a microscope that could follow single molecules. Of special interest to him was the molecular machinery that DNA uses to make copies of itself. Somewhere in their discussions arose the germ of the idea for a new way to read the alphabet that make up DNA, and to thereby access the information stored in them.

DNA (or RNA, in some viruses), the genetic material of life forms, is made of four bases (A, T, G and C; with U replacing T in the case of RNA). A chromosome is the duplex of a long linear chain of these – and in the DNA sequence is information – the blueprint of life. Life famously can replicate, and DNA replicates when an enzyme, DNA polymerase, synthesises a complementary strand using an existing DNA strand as the template.

Breakthrough idea

The breakthrough idea of Balasubramanian and Klenerman was to sequence DNA (or RNA) using this process of strand synthesis. They cleverly modified their ATGC bases so that each shone with a different colour. When copied, the “coloured” copy of DNA could be deciphered from the colours alone, using miniature optical and electronic devices.

A very significant advance in their “Next Generation Sequencing” (NGS) method lies in the size of DNA that could be sequenced at one go – more than a million base pairs can be sequenced, which translates to hundreds of genes or even the whole genome of an organism. This is made possible by simultaneously sequencing hundreds of pieces of DNA at the same time. Many copies of this long DNA “sentence” are randomly broken up into small pieces, each no more than a few hundred bases long, which are all sequenced together. The “reads” are then fitted together, in the manner of a puzzle, to give the final sequence.

This technology was spun off as a commercial entity, Solexa, with the initiative of Balasubramanian and Klenerman. This phenomenally successful startup was later acquired by the biotech company Illumina.

Falling cost

What about the cost of all this sequencing? When the Human Genome Project delivered the first, near-complete sequence of our genome, the cost was estimated to have been 3 billion dollars. As all our chromosomes together have 3 billion base pairs, it becomes an easy calculation – One dollar per sequenced base. By the year 2020, Next Generation Sequencing technologies had pushed the price for sequencing your genome down to a thousand dollars – when this technology becomes prevalent in India, this sum should become a few thousands of rupees!

To think that a coronavirus genome has not 3 billion but 30,000 RNA bases – not surprisingly, this has resulted in an explosion of data on the genomes of the novel coronavirus and its variants. Health authorities in the United Kingdom have sequenced the viral genome of one out of sixteen people who have tested Covid-positive. The popular genomic data sharing site GSAID has over two million submissions of Cov-2 genomic sequences, from 172 countries. NGS has been at the heart of monitoring the spread of viral variants across the globe, and tracing the source of outbreaks.

Shankar Balasubramanian continues to run a fine laboratory, focused on the design of therapeutic molecules that would tune down the uncontrolled expression of certain genes, and so control the damage they cause in conditions such as cancer.

3.What makes the UAPA so stringent?

How is Section 43D(5) of the law interpreted by courts and why does it make obtaining bail difficult?

The story so far: The death of Father Stan Swamy, a Jesuit priest and tribal rights activist, while in judicial custody, has brought to focus the law under which he was imprisoned. The stringent nature of the Unlawful Activities (Prevention) Act (UAPA), which renders it difficult for one held under it to obtain bail, is being seen as one of the principal reasons for Fr. Swamy’s death as a prisoner in a hospital. This has raised questions about the liberty of many others, including 15 others arrested in the Elgar Parishad case and incarcerated under the same law, which is also India’s main anti-terrorism legislation.

What is the origin of the UAPA?

The Union government was considering a stringent law against calls for secession in the mid-1960s. In March 1967, a peasant uprising in Naxalbari imparted a sense of urgency. On June 17, 1966, the President had promulgated the Unlawful Activities (Prevention) Ordinance “to provide for the more effective prevention of unlawful activities of individuals and associations”.

Its stringency created a furore in Parliament when it was tabled, leading to the government dropping it. Instead, the Unlawful Activities (Prevention) Act, 1967, which was not identical to the ordinance, was passed.

What is its scope and how has it been expanded over the years?

The Act provided for declaring an association or a body of individuals “unlawful” if they indulged in any activity that included acts and words, spoken or written, or any sign or representation, that supported any claim to bring about “the cession of a part of the territory of India”, or its “secession”, or which questions or disclaims the country’s sovereignty and territorial integrity.

Prior to the UAPA’s enactment, associations were being declared unlawful under the Criminal Law (Amendment) Act, 1952. However, the Supreme Court held that the provision on bans was unlawful because there was no judicial mechanism to scrutinise the validity of any ban. Therefore, the UAPA included provisions for a Tribunal which has to confirm within six months the notification declaring an outfit unlawful.

In its present form, the Act, after the amendments in 2004 and 2013, covers the declaration of associations as unlawful, punishment for terrorist acts and activities, acts threatening the country’s security, including its economic security (a term that covers fiscal and monetary security, food, livelihood, energy ecological and environmental security), and provisions to prevent the use of funds for terrorist purposes, including money laundering.

The ban on organisations was initially for two years, but from 2013, the period of proscription has been extended to five years.

After the Prevention of Terrorism Act (POTA), 2002, was repealed, the UAPA was expanded to include what would have been terrorist acts in earlier laws. The 2004 amendments were also aimed at giving effect to various anti-terrorism resolutions of the United Nations Security Council.

In 2012, there was a set of amendments, which was notified from early 2013, seeking to bring the UAPA in line with various requirements of the Financial Action Task Force, an inter-governmental body, to combat money laundering and terrorism financing. In 2019, the Act was amended to empower the government to designate individuals as terrorists.

How do UAPA provisions differ from regular criminal law?

Just like other special laws dealing with narcotic drugs and the now-defunct laws on terrorism, the UAPA also modifies the Code of Criminal Procedure (CrPC) to give it more teeth. A remand order can be for 30 days instead of the usual 15, and the maximum period of judicial custody before the filing of a chargesheet is extendable from the usual 90 days to 180 days. This extension, however, depends on the Public Prosecutor filing a report on the progress in the investigation and giving reasons for seeking another 90 days to complete it. The law also makes it more difficult to obtain bail.

What is the controversy about its bail provisions?

Under Section 43D(5) of the Act, bail cannot be granted to a suspect if the court is of the opinion that there are reasonable grounds to believe that the charges are prima facie true. A Supreme Court judgment on this has clarified that this meant that the court considering bail should not examine the evidence too deeply, but must go by the prosecution version based on broad probabilities. This means that the onus is on the accused to show that the case is false but without inviting the court to evaluate the available evidence. This is why human rights defenders feel that the provision is draconian, virtually rendering it impossible for anyone to obtain bail until the completion of the trial.

Why in news?

• Father Stan Swamy, arrested by the NIA in relations with Bhima Koregaon violence, passed away.
• Just 2 days before his death, he had moved the Bombay High Court challenging Section 43D(5) of the Unlawful Activities Prevention Act (UAPA).

Who is Father Stan Swamy?

• Fr. Stan Lourduswamy S.J., is an Indian Roman Catholic priest and a tribals rights activist for several decades.
• The 83-year-old activist (suffers from Parkinson’s disease) was arrested by the National Investigation Agency (NIA) in October 2020.
• He is alleged to have involved in the 2018 Bhima Koregaon violence and is charged under the UAPA.

What is Section 43D(5) of UAPA?

• The UAPA was enacted in 1967.
• It was strengthened by the Union government in 2008 and 2012.
• Section 43D(5) makes grant of bail virtually impossible under UAPA.
• It leaves little room of judicial reasoning.
• The test for denying bail under the UAPA is that the court must be satisfied that a “prima facie” case exists against the accused.
• Swamy termed Section 43D(5) as “illusory”.

What have the Courts held in this regard?

• In 2019, the SC defined prima facie narrowly to mean that the courts must not analyse evidence or circumstances.
• Instead, it should look at the “totality of the case” presented by the state.
• In other rulings, however, courts have taken an alternative reading of Section 43D(5).
• Courts have emphasised the right to a speedy trial.
• They have also raised the bar for the state to book an individual under UAPA.

What were the exceptions?

• In Union of India v K A Najeeb in January 2021, the Supreme Court upheld the grant of bail under UAPA.
• In this case,the period of incarceration already undergone has exceeded a substantial part of the prescribed sentence.
• The Court, nevertheless, recognised that bail under UAPA was an exception.

• The Court said that such an approach would act as a safeguard against Section 43D(5) of UAPA.
• Because it could be used as the sole metric for denial of bail or for wholesale breach of constitutional right to speedy trial.
• In February 2021, the Bombay High Court granted bail to Telugu poet Varavara Rao.
• He is an accused in the Elgar Parishad case along with Swamy.
• The Court, in this case, held that bail under UAPA can be granted by constitutional courts purely on grounds of sickness and advanced age.
• Rao is 80 and had tested positive for Covid-19.
• Recently, the Delhi High Court granted bail to three student-activists, circumventing the bail provision under UAPA.
• It questioned if the alleged offences qualified as “terrorist offences” to be booked under UAPA in the first place.