Subject: Biotech and Medical Sciences

The Food and Drug Administration (FDA) has approved the first vaccine ‘Arexvy’ for respiratory syncytial virus (RSV) to lower respiratory tract disease in people older than 60 years.

What is Respiratory Syncytial Virus?

• Respiratory Syncytial Virus (RSV) is a common respiratory virus that can cause illness in people of all ages.
• It is the most common cause of lower respiratory tract infections in infants and young children, and it can also affect older adults and people with weakened immune systems.
• RSV is highly contagious and spreads through droplets when an infected person coughs or sneezes, or by touching a surface contaminated with the virus and then touching one’s face.
• Symptoms of RSV can range from mild to severe, including runny nose, coughing, sneezing, fever, wheezing, and difficulty breathing.
• In severe cases, it can lead to pneumonia, bronchiolitis, or death.

Identification of Protein F

• In 2013, Barney Graham and other scientists identified the key protein, protein F, responsible for the RSV virus to infect human cells.
• The protein, introduced in humans, elicited neutralizing antibodies against the virus.

Approval and Efficacy of Arexvy

• The FDA has approved Arexvy, the first RSV vaccine to be approved anywhere in the world, manufactured by GSK.
• The approval was based on a phase-3 trial carried out on nearly 25,000 participants.
• It showed a single dose of the vaccine reduced the risk of developing lower respiratory tract disease caused by the RSV virus by 82.6% and severe disease by 94.1% in people older than 60 years.
• The vaccine will be available for older adults in the U.S. before the 2023-2024 RSV season.

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Central idea: The Kolkata-based Indian Association for the Cultivation of Science (IACS) have established the potential of quinoline derivatives to treat drug-resistant leishmaniasis, which is also called kala-azar or black fever.

What is Kala Azar?

• Kala-Azar is a vector-borne (sandfly) neglected tropical disease caused by the protozoan parasites of the genus leishmania.
• It afflicts the world’s poorest populations in over 90 countries throughout Asia, Africa, the Middle East, and Central and South America.
• Current annual estimates of kala-azar are about 1,00,000.
• More than 95% of cases reported to the WHO are from India and other tropical countries, most importantly co-infection with HIV, which leads to an immunocompromised state.

How does Quinoline work over this?

• The quinoline derivative is a potent inhibitor of an enzyme called topoisomerase 1 (LdTop1).
• This enzyme is essential for the maintenance of DNA architecture in parasites and is distinct from the one found in humans.
• Poisoning LdTop1 imparts significant cytotoxicity to both Leishmania parasites found in the gut of sandfly vectors (promastigotes) and those found in infected humans (amastigotes) of both the wild type and the antimony-resistant isolates.
• This is done without inducing lethality to human and mice host cells.

Significance of quinoline treatment

• Overcoming drug resistance in clinical leishmaniasis is a severe challenge in rural India.
• The current treatment regimens against kala-azar use formulations that are toxic and induce high levels of drug-resistance.

What is the breakthrough?

• The novel inhibitor targeting the leishmania parasites was identified by screening them against recombinant Leishmania topoisomerase 1 enzyme.
• In all, 21 derivatives were prepared and evaluated for their antileishmanial activity, and one of them was found to be effective.

Central idea: Johns Hopkins University scientists have proposed creation of Bio-Computers’ using a new area of research called “organoid intelligence”.

Background

• JHU scientists will harness the processing power of the brain and help understand the biological basis of human cognition, learning, and neurological disorders.
• Traditional methods of studying the human brain involve using rat brains, which are structurally and functionally different from human brains.

Building brain organoids in the lab

• Scientists are building 3D cultures of brain tissue in the lab, called brain organoids, using human stem cells.
• Brain organoids capture many structural and functional features of a developing human brain and are being used to study human brain development and test drugs.
• However, brain organoids developed in the lab lack sensory inputs and blood circulation, which limits their growth and sophistication.

Transplanting brain organoids

• Scientists have transplanted human brain organoid cultures into rat brains, where they formed connections with the rat brain and were functionally active.
• However, human brain organoids are still nested in the rat-brain microenvironment, which limits their relevance to humans.

What is the new “bio-computer”?

• The JHU researchers’ scheme combines brain organoids with modern computing methods to create “bio-computers”.
• Brain organoids will be grown inside flexible structures affixed with multiple electrodes to record the firing patterns of neurons and deliver electrical stimuli.
• Machine-learning techniques will be used to analyze the response patterns of neurons and their effect on human behavior or biology.

Opportunities for “bio-computers”

• Brain organoids can be developed using stem cells from individuals with neurodegenerative diseases or cognitive disorders to reveal the biological basis of human cognition, learning, and memory.
• “Bio-computers” could help decode the pathology of and develop drugs for neurodevelopmental and degenerative diseases such as Parkinson’s disease and microcephaly.

Challenges for bio-computers

• Brain organoids have a diameter of less than 1 mm and have fewer than 100,000 cells on average, limiting their computing capacity.
• Researchers will have to develop microfluidic systems to transport oxygen and nutrients and remove waste products.
• The hybrid systems will generate large amounts of data that will need to be stored and analyzed using “Big Data” infrastructure and advanced analytical techniques.
• An ethics team is proposed to identify, discuss, and analyze ethical issues as they arise in the course of this work.

Conclusion

• Biocomputers will harness the processing power of the brain and help understand the biological basis of human cognition, learning, and various neurological disorders.
• Scaling up brain organoids and developing microfluidic systems and analytical techniques are the key challenges.
• Ethical issues arising from the development of biocomputers will be analyzed by an ethics team.

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Central idea: This article discusses recent developments in the field of HIV research that have led to the possibility of a cure for the disease.

What is HIV/AIDS?

• HIV (human immunodeficiency virus) is a virus that attacks cells that help the body fight infection, making a person more vulnerable to other infections and diseases.
• First identified in 1981, HIV is the cause of one of humanity’s deadliest and most persistent epidemics.
• It is spread by contact with certain bodily fluids of a person with HIV, most commonly during unprotected sex, or through sharing injection drug equipment.
• If left untreated, HIV can lead to the disease AIDS (acquired immunodeficiency syndrome).
• The human body can’t get rid of HIV and no effective HIV cure exists.

Present treatment of HIV

• However, by taking HIV medicine (called antiretroviral therapy or ART), people with HIV can live long and healthy lives and prevent transmitting HIV to their sexual partners.
• In addition, there are effective methods to prevent getting HIV through sex or drug use, including pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).

What is the new breakthrough?

• Doctors selected a donor carrying two copies of a CCR5-delta 32 genetic mutation – a mutation that is known to make the carriers almost immune to HIV.
• The CCR5-delta 32 genetic mutation is a rare genetic mutation that affects the CCR5 gene, which is involved in the immune system’s response to infection.
• The mutation causes a deletion of 32 nucleotides in the gene, resulting in a truncated or shortened version of the CCR5 protein.
• This truncated protein is not able to function normally, and people with this mutation are largely resistant to HIV infection.

How has the CCR5-delta 32 mutation been used in HIV research?

• Researchers have been studying the CCR5-delta 32 mutation as a potential avenue for developing an HIV cure.
• One approach involves using gene editing technologies like CRISPR to induce the mutation in HIV-positive individuals, effectively making their immune cells resistant to HIV infection.
• Another approach involves bone marrow transplantation from donors with the CCR5-delta 32 mutation.

What are the risks associated?

• Gene editing technologies like CRISPR are still in their early stages, and there are concerns about the safety and effectiveness of these methods.
• Additionally, bone marrow transplantation is a complex and risky procedure that is not feasible for all HIV-positive individuals.
• Finally, it is important to note that not all HIV infections are caused by the CCR5 strain of the virus, and therefore the use of the CCR5-delta 32 mutation as an HIV cure would not be effective for all cases of HIV.

Prevalence of HIV/AIDS in India

• As per the India HIV Estimation 2019 report, the estimated adult (15 to 49 years) HIV prevalence trend has been declining in India since the epidemic’s peak in the year 2000 and has been stabilizing in recent years.
• In 2019, HIV prevalence among adult males (15–49 years) was estimated at 0.24% and among adult females at 0.20% of the population.
• There were 23.48 lakh Indians living with HIV in 2019.
• Maharashtra had the maximum at 3.96 lakh followed by Andhra Pradesh (3.14 lakh) and Karnataka.
• ART is freely available to all those who require and there are deputed centres across the country where they can be availed from.

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Central idea: Equatorial Guinea has confirmed its first-ever outbreak of Marburg virus disease.

Marburg Virus

• The Marburg virus is a highly dangerous pathogen that targets several organs and reduces the body’s ability to function on its own.
• Depending on the strain and case management, the fatality rates for the virus range from 24% to 88%.

Transmission and Prevention

• The natural carrier of the Marburg virus is the African fruit bat, which carries the virus but does not fall sick from it.
• Human-to-human transmission occurs through contact with blood or other bodily fluids.
• Rehydration treatment to alleviate symptoms can improve the chances of survival.

Its outbreaks

• The virus has caused simultaneous outbreaks of disease in laboratories in Marburg, Germany and Belgrade, Serbia in 1967, resulting in seven deaths.
• During an outbreak in Angola in 2004, the virus killed 90% of the 252 people who were infected, and in Ghana last year, two people died of Marburg.

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https://indianexpress.com/article/explained/explained-health/equatorial-guinea-confirms-marburg-virus-outbreak-explained-8443753/

The new CAR T-Cell Immunotherapy holds promise for Ovarian Cancer patients over other forms of treatment.

What are CAR T-cells?

• Chimeric antigen receptor (CAR) T-cell therapies represent a quantum leap in the sophistication of cancer treatment.
• Unlike chemotherapy or immunotherapy, which require mass-produced injectable or oral medication, CAR T-cell therapies use a patient’s own cells.
• They are modified in the laboratory to activate T-cells, a component of immune cells, to attack tumours.
• These modified cells are then infused back into the patient’s bloodstream after conditioning them to multiply more effectively.
• The cells are even more specific than targeted agents and directly activate the patient’s immune system against cancer, making the treatment more clinically effective.
• This is why they’re called ‘living drugs’.

How does the therapy work?

• In CAR T-cell therapy, the patient’s blood is drawn to harvest T-cells which are immune cells that play a major role in destroying tumour cells.
• Researchers modify these cells in the laboratory so that they express specific proteins on their surface, known as chimeric antigen receptors (CAR).
• They have an affinity for proteins on the surface of tumour cells.
• This modification in the cellular structure allows CAR T-cells to effectively bind to the tumour and destroy it.
• The final step in the tumour’s destruction involves its clearance by the patient’s immune system.

Where is it used?

• As of today, CAR T-cell therapy has been approved for leukaemias (cancers arising from the cells that produce white blood cells) and lymphomas (arising from the lymphatic system).
• These cancers occur through the unregulated reproduction of a single clone of cells, that is, following the cancerous transformation of a single type of cell, it produces millions of identical copies.
• As a result, the target for CAR T-cells is consistent and reliable.
• CAR T-cell therapy is also used among patients with cancers that have returned after an initial successful treatment or which haven’t responded to previous combinations of chemotherapy or immunotherapy.
• Its response rate is variable. In certain kinds of leukaemias and lymphomas, the efficacy is as high as 90%, whereas in other types of cancers it is significantly lower.

How widespread is its use?

• The complexity of preparing CAR T-cells has been a major barrier to their use.
• The first clinical trial showing they were effective was published almost a decade ago; the first indigenously developed therapy in India was successfully performed only in 2022.
• The technical and human resources required to administer this therapy are also considerable.
• Treatments in the US cost more than a million dollars.
• Trials are underway in India, with companies looking to indigenously manufacture CAR T-cells at a fraction of the cost.
• The preliminary results have been encouraging.

What are conventional cancer therapies?

• The three major forms of treatment for any cancer are surgery (removing the cancer), radiotherapy (delivering ionising radiation to the tumour), and systemic therapy (chemotherapy- administering medicines that act on the tumour only).
• Surgery and radiotherapy have been refined significantly over time whereas advances in systemic therapy have been unparalleled.
• A new development on this front, currently holding the attention of many researchers worldwide, is the CAR T-cell therapy.

Will this therapy be expensive in India as well?

• In India, introducing any new therapy faces the twin challenges of cost and value.
• Critics argue that developing facilities in India may be redundant and/or inappropriate as even when it becomes cheaper, CAR T-cell therapy will be unaffordable to most Indians.
• Those who are affluent and require the therapy currently receive it abroad anyway.
• While this is true, it may be the right answer to the wrong question.
• Having access to a global standard of care is every patient’s right; how it can be made more affordable can be the next step.

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A slew of recent studies has shown that a phenomenon in our bodies, called immune imprinting, might be making new boosters vaccines far less effective than expected for coronavirus infection.

What is Immune Imprinting?

• Immune imprinting is a tendency of the body to repeat its immune response based on the first variant it encountered.
• Our body does this through infection or vaccination — when it comes across a newer or slightly different variant of the same pathogen.
• The phenomenon was first observed in 1947, when scientists noted that “people who had previously had flu, and were then vaccinated against the current circulating strain, produced antibodies against the first strain.
• At the time, it was termed the ‘original antigenic sin’ but today, it’s commonly known as imprinting.

How imprinting works for immune system?

• Imprinting acts as a database for the immune system, helping it put up a better response to repeat infections.
• After our body is exposed to a virus for the first time, it produces memory B cells that circulate in the bloodstream and quickly produce antibodies whenever the same strain of the virus infects again.
• The problem occurs when a similar, not identical, variant of the virus is encountered by the body.
• In such cases, the immune system, rather than generating new B cells, activates memory B cells.
• This in turn produce antibodies that bind to features found in both the old and new strains, known as cross-reactive antibodies.

Are the booster doses completely useless?

• These cross-reactive antibodies do offer some protection against the new strain,.
• However they are not as effective as the ones produced by the B cells when the body first came across the original virus.

How to circumvent immune imprinting?

• Currently, several ongoing studies are trying to find a way to deal with imprinting.
• Some scientists have said nasal vaccines might be better at preventing infections than injected ones.
• They believe the mucous membranes would create stronger protection, despite carrying some imprint of past exposure.
• Researchers are also trying to find if spacing out coronavirus vaccine shots on an annual basis, could help with the problem of imprinting.

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