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वैक्सीन की अगली पीढ़ी

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वैक्सीन की शक्ति

Since their invention in the 19th century, vaccines have been a massive healthcare revolution. In part, they drastically reduced mortality from deadly diseases, with no less पिछले 50 वर्षों में विश्व स्वास्थ्य संगठन (WHO) के अनुसार 154 मिलियन से अधिक जीवन बचाए गए.

Vaccines have also entirely eradicated the terrible disease that was smallpox, जिसे अनुमानित रूप से अपनी 100 वर्षों की अवधि में 500 मिलियन लोगों की मौत का कारण माना गया है.

The next on the chopping block might be polio, with the last pockets of endemic polio in Pakistan and Afghanistan. Polio used to kill half a million people every year before vaccination.

स्रोत: स्रोत: Delaware Journal Of Public Health

And, of course, the recent pandemic has seen vaccine and anti-vaccine movements at the forefront of the public discourse, with mRNA vaccine technology making a spectacular entry into the market and public awareness.

Despite these successes, infectious diseases still account for around 40% of all recorded deaths in the world. In part, this is due to insufficient vaccination coverage in poor developing countries, but it is also due to some diseases still resisting the effort to develop vaccines against them.

This might change thanks to many new technologies converging into creating a new generation of vaccines.

स्रोत: Phrma

वैक्सीन कैसे काम करते हैं

The base principle of a vaccine is to “train” the immune system before it encounters a dangerous disease caused by a virus or bacteria (पैथोजन).

This works by presenting to the body either part of the pathogenic (“disease-causing”) bacteria or virus (the antigen) or the full pathogen, which is either killed or weakened so it cannot cause the disease.

When it is done, the body’s immune system starts developing proteins called antibodies. These antibodies “click” to specific parts of the pathogen or antigen, recognizing it in the same way a key and lock work.

स्रोत: Cusabio

It is the specificity of the antigen-antibody interaction that allows for the antibody to neutralize the pathogen and protect the person against the disease.

You can also watch this 3min video animating these base principles of vaccination:

For some diseases, like smallpox, this worked so well that we managed to fully exterminate the disease.

But others are trickier. Here are some of the methods pathogens can use to escape vaccines and the immune system:

  • बहुत परिवर्तनशील एंटीजन। यह रणनीति फ्लू और सामान्य सर्दी वायरस द्वारा उपयोग की जाती है, जिनमें इतने कई वैरिएंट होते हैं कि हर साल मौसमी फ्लू वैक्सीन और प्रतिरक्षा प्रणाली के दृष्टिकोण से एक “नया” रोग बन जाता है।
  • कम सांद्रता और छिपना. कुछ रोग प्रतिरक्षा प्रणाली से बहुत अच्छी तरह छिप जाते हैं। वे आमतौर पर क्रॉनिक रोग पैदा करते हैं, लेकिन यदि प्रतिरक्षा प्रणाली उन्हें नहीं ढूँढ पाती, तो वैक्सीन कम उपयोगी होती है या बिल्कुल काम नहीं कर सकती।
  • प्रतिरक्षा प्रणाली को निष्क्रिय करना. सबसे प्रमुख रूप से, यह वही तरीका है जिससे HIV काम करता है, जो सीधे शरीर की एंटीबॉडी‑उत्पादन प्रणाली पर हमला करता है।
  • तेज़ी से हमला करना. कुछ रोग इतनी तेज़ी से प्रकट होते हैं कि शरीर के पास प्रतिक्रिया करने और पर्याप्त एंटीबॉडी बनाने का समय नहीं रहता। यह विशेष रूप से बहुत आक्रामक और घातक रोगों जैसे ईबोला में समस्या है।

वैक्सीन के अगले लक्ष्य

दीर्घकालिक संक्रमण

As mentioned above, a segment of diseases that have overall resisted efforts to develop vaccines are chronic diseases.

Because these diseases evolved to create an infection that stays below a threshold that would trigger an efficient immune response, it is hard to create a vaccine that works. This includes a few major global killers.

मलेरिया

There were 249 million cases of malaria in 2022, causing around 600,000 deaths per year, with most of them children under 5 years old. This is also a very debilitating disease, leading to missed school and work days, loss of energy, income, and economic opportunities, altogether a cause of and made worse by poor economic conditions.

For example, in Mozambique, malaria was the cause of 45% of outpatient consultations and 24% of hospital admissions in 2015.

“साधारण मलेरिया से जुड़ी औसत घर खर्च ज़ाम्बेज़िया में एक परिवार के मासिक खर्च का 10% (US$ 1.63) से 21% (US$ 3.46) तक दर्शाता है, जबकि गंभीर मामले की लागत (US$ 64.90 और US$ 81.08) प्रति व्यक्ति औसत मासिक खर्च से तीन गुना से अधिक है।”

Malaria Journal

Malaria is caused by a parasite that hides in the patient’s liver and is transmitted through mosquito bites. It also has more than 60 variable antigen genes and switches between them to hide further from the immune system.

Until recently, a malaria vaccine has been difficult to develop, leading to the main effort to control the diseases focused on targeting the mosquitoes instead. Drugs are also a possibility, but the parasite tends to develop resistance against previously efficient molecules.

अंत में उपलब्ध वैक्सीन

In 2021, the WHO recommended for widespread use of the RTS, a malaria vaccine for children in affected areas, produced by pharmaceutical giant GSK. In 2023, a second malaria vaccine (R21/Matrix-M), created by the University of Oxford, was approved.

Both approved malaria vaccines do not fully avoid the disease, but radically reduce the severity of the symptoms and the risk of death. These vaccines use artificial proteins and virus-like particles.

Among the candidates for new, more efficient vaccines are the PfSPZ vaccine in development by Sanaria. It is now in Phase 2 of clinical trials and uses a genetically modified version of the whole parasite.

“Only Sanaria’s P. falciparum sporozoite vaccines have achieved >90% vaccine efficacy against controlled human malaria infections”

Sanaria

 HIV/AIDS

HIV, the virus causing AIDS, was infecting 39 million people in 2022, causing 630,000 deaths. While patients can see lower mortality and higher quality of life by using anti-HIV drugs, a cure and eradication of the disease will likely require a vaccine.

By attacking the CD4 cells, a part of the immune system, the virus manages to avoid detection until it is too late.

A vaccine has been very difficult to develop, and it is still unclear what will work.

Among the notable efforts and potential cures in development are:

अन्य

It would be too long to cover all the existing vaccine initiatives. You can read more इस 11‑पृष्ठीय रिपोर्ट में इसके बारे में.

Among the other important diseases with active efforts made to develop a vaccine against them are:

  • डेंगी
  • हुकवर्म
  • लीशमैनीयासिस
  • साइटोमेगालोवायरस (हर्पीस)
  • लाइम रोग
  • शिंगल्स

आक्रामक संक्रमण

New diseases and aggressive patterns of infection can overwhelm the immune system and lead to very high death rates in infected patients.

One example is Ebola and other hemorrhagic fevers, with death rates in the 30-50%. There are currently 2 Ebola vaccines, Merck’s Ervebo approved in 2019, and Johnson & Johnson’s (JNJ ) Zabdeno+Mvabea.

Of course, another example is coronavirus, the cause of the COVID-19 pandemic, but also of the previous deadly outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) and 2002-2004 Severe acute respiratory syndrome (SARS).

नई वैक्सीन तकनीक

Previous generations of vaccines were based on a few techniques, like using a weakened part of the virus/bacteria, a dead full-version of it, just fragments, or more recently the antigen expressed into another vector through genetic modification.

Modern biosciences are now coming with many new potential modes of vaccination.

mRNA वैक्सीन

Widely promoted and very quickly adopted because of the COVID-19 pandemic, mRNA vaccines have a powerful advantage over traditional vaccines.

Instead of slowly finding how to safely inactivate a virus, or how to efficiently modify another vector, it can directly “program” a cure in just 3-4 weeks. This is because the mRNA code can be directly written once the targeted virus genome is known, something that was achieved in the very first week of Covid-19 identification.

Other COVID vaccines existed during the pandemic, but the quick development cycle of mRNA vaccines made it the perfect solution for a novel disease.

More mRNA vaccines are now in development, especially by the 2 companies that benefited the most from the mRNA vaccines’ sales during the pandemic.

न्यूक्लिक एसिड वैक्सीन

While technically, mRNA vaccines are a sub-category of nucleic acid vaccines, the technology is broader and includes a few other potential types of vaccines.

The first one is DNA vaccines, which use a molecule of DNA instead of RNA. Over 160 different DNA vaccines are currently being tested in human clinical trials in the United States. अनुमान है कि इन ट्रायलों में से 62% कैंसर वैक्सीन के लिए और 33% मानव इम्यूनोडेफ़िशिएंसी वायरस (HIV) के खिलाफ वैक्सीन के लिए समर्पित हैं।

खेतों में वैक्सीन उगाना

We are used to thinking of vaccines as full or parts of a virus/bacteria. Even antigen-based vaccines are produced by multiplying this antigen in unicellular organisms.

But this might change with the progress of genetic modification, with the hope to one day produce vaccine material the way we grow food.

Plant-based vaccines could be growing the vaccine component in open fields or greenhouses. This would radically reduce production costs.

The issue is that most antigens will not be produced in plants the way they would in bacteria or viruses, due to different cellular biochemistry, notably the sugars added to proteins.

A more promising field than growing vaccines in plants like corn or wheat is using microalgae. The technology is now starting to be used for animal vaccines, and माइक्रोएल्गी की कोशिका दीवार एक पूर्व-स्थापित “कैप्सूल” प्रदान करती है जिससे वैक्सीन को शुद्धिकरण और इंजेक्शन की आवश्यकता के बिना खाने योग्य बनाता है

ऑर्गेनोपार्टिकल्स

Changing the fundamental technology of vaccine production is not the only way to improve vaccines.

For example, most vaccines use “adjuvants,” chemical compounds that boost the immune system. However, these can cause unwanted side effects as they stimulate ALL immune reactions, not just the ones intended by the vaccine.

Instead, a recent publication by a research team from MIT might have found a solution to increase vaccine effectiveness by using a novel type of adjuvant leveraging nanotechnology.

They used a metal-organic framework (MOF) nanoparticle, which acts as an adjuvant, boosting a specific immune reaction instead of a generalized reaction like with classical adjuvants. We discussed this discovery in more detail in our article “धातु‑कार्बनिक नैनोकणों के माध्यम से वैक्सीन की प्रभावशीलता बढ़ाना”

मिश्रित फ्लू शॉट

A more powerful or quicker development cycle might still leave highly variable viruses like the seasonal flu free from a perfectly efficient vaccine.

This is because these vaccines target antigens that are highly variable, allowing the virus to quickly escape the acquired immunity.

Researchers are now finding that they can force the immune system to focus on other, less variable sections of the virus. We discussed how this was done by combining 80,000 mutated versions of the flu virus in our article “फ्लू शॉट्स को अंधेरे में शूट किया जा सकता है – वैज्ञानिक नई दृष्टिकोण पर प्रकाश डालने की कोशिश कर रहे हैं”.

बेहतर लॉजिस्टिक्स और डिलीवरी

Other improvements that could be made regarding vaccines are related to logistics and methods of administration. A lot of vaccination campaigns come from logistics, cold storage, the need for medical professionals to inject the vaccine, etc.

For example, कैम्ब्रिज के शोधकर्ताओं ने वायरल कणों को शुगर ग्लास की अल्ट्रा‑थिन परत में फँसाने का तरीका खोजा, जिससे छह महीने तक 113°F तक के तापमान पर भंडारण संभव हो गया.

As discussed above, an algae-based vaccine could be delivered orally, like a vitamin pill.

Another option could be वैक्सीन माइक्रोएरे पैच (vaccine-MAPs), also known as microneedle patches. This injection-free option is painless and could improve both logistic challenges and compliance while making the administration of vaccines quicker.

डिजिटल वैक्सीन रिकॉर्ड

Lastly, technology could help monitor the vaccination status of individual people and the whole population. Digital records can help decision-makers design better vaccination campaigns, anticipate epidemics, and improve vaccination rates.

गैर‑संचारी रोगों के वैक्सीन

While probably not technically “vaccines,” there are many new vaccine-like treatments in development looking to prevent death by modifying the body’s chemistry or immune system.

कैंसर वैक्सीन

As cancer is quickly becoming a larger cause of death than infectious disease worldwide, better treatments are becoming increasingly important.

Technically, some cancer vaccines already exist for cancers induced by infectious diseases, like HPV and Hepatitis B.

Another category is therapeutic cancer vaccines. They are looking to make the immune system react to cancer cells the way it would to an infectious pathogen.

This is done by inducing the immune reaction against antigens present in the cancer cells.

Already, several cancer vaccines have been approved for प्रोस्टेट और ब्लैडर कैंसर, साथ ही मेलेनोमा.

लगभग हर प्रकार के कैंसर के लिए और भी विकास में हैं, especially the ones resistant to currently available therapies, like pancreas cancer.

एंटी‑एजिंग वैक्सीन

One possibility to fight aging is creating induced-Pluripotent Stem (iPS) cells, with massive potential to repair and rejuvenate the body’s tissues. This reprogramming could be achieved through a transient genetic reprogramming, relying on an mRNA-based method.

This method is very similar to the mRNA vaccines, except the target is not to create immunity but to temporarily modify the targeted cell.

We look at transient cellular reprogramming and other anti-aging potential technologies in our article “बुढ़ापा जीवन का हिस्सा है – इसका मतलब यह नहीं कि हम लड़ नहीं सकते”.

अल्ज़ाइमर वैक्सीन

With the population aging, Alzheimer’s is a growing public health concern.

The American company Vaxxinity reported successful phase 2 trials of UB-311, targeting toxic amyloid beta forms in the brain, which not only triggered an immune response but also demonstrated safety.

कई अन्य संभावित अल्ज़ाइमर वैक्सीन परीक्षण में हैं, with others targeting the amyloid proteins, as well as targeting the tau protein, or inflammation.

डायबिटीज़

Type-1 diabetes is an autoimmune disease where the body’s immune system targets the insulin-making cells in the pancreas. So it makes sense that a “vaccine” modulating immunity could potentially prevent this disease.

Macrogenics’ TZIELD 2022 में स्वीकृत हुआ and reduces the risk of developing type-1 diabetes. While not foolproof, this is a massive step into one day fully avoiding the disease developing or reversing the damages it causes.

सूजन वैक्सीन

A vaccine targeting human cytokines, a key factor in asthma, was invented in 2023. Other “vaccines” (really monoclonal antibodies) targeting psoriasis are also in development.

Similar progress in managing inflammation and autoimmune disorders is ongoing, with many vaccine candidates targeting cytokines as well, which include:

वैक्सीन कंपनियां

1. BioNTech (BTNX)

BioNTech is doubling down on the technology that forms the core of its business. The company behind the Covid mRNA vaccine sold by Pfizer is now using the money made during the pandemic to widely expand its offer.

It is now developing mRNA vaccines for shingles, tuberculosis, malaria, HIV, and the herpes virus. This makes it a leading company in the field of mRNA vaccines, with only its competitor Moderna (MRNA) developing more mRNA vaccines than BioNTech.

BioNTech is also exploring the potential of mRNA for cancer, with  12 different candidate products for cancer treatment in its pipeline.

स्रोत: BioNTech

Finally, it also has in its R&D pipeline some cell therapies and other non-mRNA potential cancer treatments.

mRNA has been a revolution in therapy for viral infection. BioNTech is counting on mRNA being an equally massive revolution in oncology.

With a presence in the whole spectrum of mRNA vaccine potential, both for infectious diseases and for cancer, BioNTech provides investors with exposure to both.

2. Immatics

IMTX मूल्य चार्ट

Immatics प्रतिरक्षा प्रणाली को पुनः‑प्रोग्राम करके कैंसर कोशिकाओं को लक्षित करने की कोशिश कर रहा है, जिससे यह कैंसर “वैक्सीन” में अग्रणी बन रहा है, जिसे TCR थैरेपी भी कहा जाता है।

दो मूलभूत चरण आवश्यक हैं:

  • ट्यूमर पर स्वाभाविक और विशिष्ट रूप से महत्वपूर्ण स्तर पर अभिव्यक्त एक वास्तविक कैंसर लक्ष्य का चयन करना।
  • सही, शक्तिशाली TCR विकसित करना जो चयनित कैंसर लक्ष्य को विशेष रूप से पहचानता हो, और स्वस्थ टिश्यूज़ के साथ न्यूनतम या कोई क्रॉस‑रिएक्टिविटी न रखता हो।

स्रोत: Immatics

The company’s R&D pipeline is split between therapies where the cells are collected for each patient (autologous) and “off-the-shelf” therapies (heterologous).

The company has established a strong line-up of partnerships, including with BMS, Moderna, and Editas.

स्रोत: Immatics

Moderna के साथ “रणनीतिक मल्टी‑प्लेटफ़ॉर्म सहयोग” के लिए साझेदारी 2023 के अंत में स्थापित की गई थी।

Immatics के उत्पाद अभी भी प्रारंभिक चरण में हैं लेकिन उनका विशाल संभावनाएँ हैं, जिसे उद्योग के नेताओं जैसे BMS और Moderna ने स्पष्ट रूप से मान्यता दी है।

कंपनी की उम्मीदवार थैरेपीज़ मेलेनोमा और अंडाशय, फेफड़े, गर्भाशय, ब्लैडर, सिर और गर्दन, तथा अन्य ठोस कैंसर प्रकारों में कैंसर को लक्षित करती हैं।

निष्कर्ष

Vaccination has changed the world, saving hundreds of millions of lives. And it might soon have an equally large impact, potentially wiping out deadly diseases that have plagued humankind for eons.

We might also see relatively soon the emergence of new vaccine types. Some will leverage new technologies to target diseases so far not targeted by vaccines. Or to make vaccines that would be injection-free, painless, edible, cheaper, and that could be stored at room temperature.

Finally, our deepening understanding of the immune system and the mechanics of inflammation might open the way to “quasi-vaccines” preventing or curing diseases as varied as Alzheimer’s, asthma, or diabetes.

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जॉनाथन एक पूर्व बायोकेमिस्ट शोधकर्ता हैं, जिन्होंने आनुवंशिक विश्लेषण और क्लिनिकल परीक्षणों में काम किया। वह अब एक स्टॉक विश्लेषक और वित्तीय लेखक हैं, जो नवाचार, बाजार चक्र और भू-राजनीति पर अपने प्रकाशन 'The Eurasian Century' में केंद्रित हैं।