Adjuvant Developed with NIH Funding Enhances Efficacy of India’s COVID-19 Vaccine

An adjuvant developed with funding from the National Institutes of Health has contributed to the success of the highly efficacious COVAXIN COVID-19 vaccine, which roughly 25 million people have received to date in India and elsewhere. Adjuvants are substances formulated as part of a vaccine to boost immune responses and enhance a vaccine’s effectiveness. COVAXIN was developed and is manufactured in India, which is currently suffering a devastating health crisis due to COVID-19. 

“Ending a global pandemic requires a global response,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “I am pleased that a novel vaccine adjuvant developed in the United States with NIAID support is part of an efficacious COVID-19 vaccine available to people in India.” 

The adjuvant used in COVAXIN, Alhydroxiquim-II, was discovered and tested in the laboratory by the biotech company ViroVax LLC of Lawrence, Kansas with support exclusively from the NIAID Adjuvant Development Program. The adjuvant comprises a small molecule attached in a unique way to Alhydrogel, a substance frequently called alum that is the most commonly used adjuvant in vaccines for people. Alhydroxiquim-II travels to lymph nodes, where the small molecule detaches from alum and activates two cellular receptors. These receptors, TLR7 and TLR8, play a vital role in the immune response to viruses. Alhydroxiquim-II is the first adjuvant in an authorized vaccine against an infectious disease to activate TLR7 and TLR8. In addition, the alum in Alhydroxiquim-II stimulates the immune system to search for an invading pathogen.

Molecules that activate TLR receptors stimulate the immune system powerfully, but the side effects of Alhydroxiquim-II are mild. This is because, after COVAXIN is injected, the adjuvant travels directly to nearby lymph nodes, which contain white blood cells that play an essential role in identifying pathogens and fighting infection. Consequently, only a small amount of Alhydroxiquim-II is needed in each dose of vaccine, and the adjuvant does not circulate throughout the body, thereby averting more widespread inflammation and undesirable side effects. 

COVAXIN comprises a disabled form of SARS-CoV-2 that cannot replicate but still stimulates the immune system to make antibodies against the virus. Published results from a Phase 2 trial of the vaccine indicate that it is safe and well tolerated. Safety data from a Phase 3 trial of COVAXIN in 25,800 participants in India will become available later this year. Meanwhile, unpublished interim results from the Phase 3 trial indicate that the vaccine has 78% efficacy against symptomatic disease, 100% efficacy against severe COVID-19, including hospitalization, and 70% efficacy against asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19. Results from two studies of blood serum from people who had received COVAXIN suggest that the vaccine generates antibodies that effectively neutralize the B.1.1.7 (Alpha) and B.1.617 (Delta) variants of SARS-CoV-2, first identified in the United Kingdom and India, respectively. 

The NIAID Adjuvant Program has supported the research of the founder and chief executive officer of ViroVax―Sunil David, M.D., Ph.D.―since 2009. His work has focused on searching for novel molecules that activate innate immune receptors and developing them as vaccine adjuvants. 

The collaboration between Dr. David and the company that makes COVAXIN, Bharat Biotech International Ltd. of Hyderabad, was initiated during a 2019 meeting in India coordinated by the NIAID Office of Global Research under the auspices of NIAID’s Indo-U.S. Vaccine Action Program. A delegation of five NIAID-funded adjuvant investigators including Dr. David; two members of the NIAID Division of Allergy, Immunology, and Transplantation; and the NIAID India representative visited four leading biotechnology companies to learn about their work and discuss potential collaborations. The delegation also attended a consultation in New Delhi co-organized by NIAID and India’s Department of Biotechnology and hosted by India’s National Institute of Immunology.

Among the scientific collaborations sparked by these activities, Bharat Biotech signed a licensing agreement with Dr. David to use Alhydroxiquim-II in their candidate vaccines. This license was expanded during the COVID-19 pandemic to include COVAXIN, which has received Emergency Use Authorization in India and more than a dozen other countries. Bharat Biotech developed COVAXIN in collaboration with the Indian Council of Medical Research ‒ National Institute of Virology. The company conducted extensive safety studies of Alhydroxiquim-II and undertook the complex process of scaling up production of the adjuvant under Good Manufacturing Practice standards. Bharat Biotech expects to produce an estimated 700 million doses of COVAXIN by the end of 2021.

First ever village-level mapping of childhood undernutrition in India reveals sharp local disparities

The study is the first to predict and map the burden of childhood undernutrition across all of the nearly 600,000 villages in rural India, and the methods developed to do so could be applied to other health indicators and help advance the field of “precision public health,” in which interventions and policies are tailored to smaller populations that are disproportionally affected by specific health issues, according to the study’s authors.

“By applying state-of-the-art data science techniques to existing public health indicators and census data, we created a framework that we hope can help local and regional decision makers better understand the substantial village disparities in childhood undernutrition,” said S.V. Subramanian, corresponding author and professor of population health and geography at Harvard Chan School. “Mahatma Gandhi once said that India lives in its villages. Now we can bring the power of data science to aid public policy thru precision targeting and help ensure that children in all of India’s villages are given an opportunity to grow healthy and thrive.”

The study was published April 26, 2021, in the Proceedings of the National Academy of Sciences.

Childhood undernutrition is a major problem in India; the country accounts for almost one-third of the global prevalence of childhood stunting. Precisely identifying areas with high levels of undernutrition, however, can be difficult because childhood nutrition data—and other key public health data—is typically analyzed at the district level. There are 640 districts in India per the 2011 census, a district can cover hundreds of square miles, and each district has an average rural population of 1.3 million people. Studying childhood nutrition data at this scale can result in oversimplified or misleading analyses that overlook substantial disparities within a district. Moreover, this approach can foster a lack of political accountability for the agencies responsible for crafting and implementing policies and interventions.

To obtain a more granular understanding of childhood undernutrition, the research team focused on India’s 597,121 inhabited census villages. Villages are the smallest unit of governance in India, and the researchers said that mapping and analyzing nutrition data at the village level could provide a more accurate understanding of childhood health and result in more informed and effective local politics in India.

The team combined data from numerous sources including the 2011 census and the 2016 Indian Demographic and Health Survey, which contained anonymized GPS data on approximately 20,000 “clusters,” or villages or groups of villages. The researchers then created a machine-learning prediction model to extrapolate the available data and estimate the prevalence of key indicators of undernutrition, including stunting, underweight, and wasting, for every village in the country.

The findings showed substantial variations in undernutrition across villages. For instance, the average predicted rate of stunting across all villages was 37.9%. In 691 villages, however, the average predicted rate of stunting was under 5%, while it exceeded 70% in 453 villages. In all districts, the authors noted, they found a mix of villages with high and low burdens of undernutrition.

The authors said the village-level model they created could potentially shift the paradigm of policy discussions in India by enabling policy makers and public health officials to better prioritize villages struggling with a high burden of undernutrition. The authors also created a publicly available dashboard that allows users to explore the village maps and associated data in an interactive manner.

“We focused on India, but this approach can be developed and applied to other countries to predict local health, nutrition and population estimates and better understand disparities,” said first author Rockli Kim, assistant professor at Korea University and a visiting scientist at the Harvard Center for Population and Development Studies.

WHO lists two additional COVID-19 vaccines for emergency use and COVAX roll-out

The World Health Organization (WHO) on Monday listed two versions of the AstraZeneca/Oxford COVID-19 vaccine for emergency use, giving the green light for these vaccines to be rolled out globally through COVAX. The vaccines are produced by AstraZeneca-SKBio (Republic of Korea) and the Serum Institute of India.

WHO’s Emergency Use Listing (EUL) assesses the quality, safety and efficacy of COVID-19 vaccines and is a prerequisite for COVAX Facility vaccine supply. It also allows countries to expedite their own regulatory approval to import and administer COVID-19 vaccines.

“Countries with no access to vaccines to date will finally be able to start vaccinating their health workers and populations at risk, contributing to the COVAX Facility’s goal of equitable vaccine distribution,” said Dr Mariângela Simão, WHO Assistant-Director General for Access to Medicines and Health Products.

‘But we must keep up the pressure to meet the needs of priority populations everywhere and facilitate global access. To do that, we need two things – a scale-up of manufacturing capacity, and developers’ early submission of their vaccines for WHO review.”

The WHO EUL process can be carried out quickly when vaccine developers submit the full data required by WHO in a timely manner. Once those data are submitted, WHO can rapidly assemble its evaluation team and regulators from around the world to assess the information and, when necessary, carry out inspections of manufacturing sites.

In the case of the two AstraZeneca/Oxford vaccines, WHO assessed the quality, safety and efficacy data, risk management plans and programmatic suitability, such as cold chain requirements. The process took under four weeks.

The vaccine was reviewed on 8 February by WHO’s Strategic Advisory Group of Experts on Immunization (SAGE), which makes recommendations for vaccines’ use in populations (i.e. recommended age groups, intervals between shots, advice for specific groups such as pregnant and lactating women). The SAGE recommended the vaccine for all age groups 18 and above. 

The AstraZeneca/Oxford product is a viral vectored vaccine called ChAdOx1-S [recombinant]. It is being produced at several manufacturing sites, as well as in the Republic of Korea and India. ChAdOx1-S has been found to have 63.09% efficacy and is suitable for low- and middle-income countries due to easy storage requirements

Rural women in India go digital to manage the pandemic’s disruptions

Women artisans from Barara village in Gujarat’s Patan district doing traditional embroidery.

Muskanben Vohara and her group of women weavers in Gujarat’s Anand district were overcome with worry when the lockdown was announced to contain the Covid-19 pandemic.

“I look after eight members of my family,” said the 20-year-old on a video call from her village home. “All our work had come to a grinding halt. How would we survive?”  

Luckily, Muskanben and her group had just been trained in digital skills by the Self-Employed Women’s Association (SEWA), a membership-based organization that seeks to improve the lives and livelihoods of women who work in the informal sector, including seamstresses, artisans, vendors, and small and marginal farmers.Our Leelawati project proved timely. When we first launched it, traditional occupations were being buffeted by globalization, liberalization and other economic changes. Little did we realize how useful the training would become during the pandemic.Reema NanavatySEWA’s Director

Armed with the training, the group was soon able to share photographs of their products online, create Whatsapp groups of customers, and enable digital payments for purchases.

“Not only were we able to continue our work uninterrupted,” declared Muskanben proudly, “we sold off all our stocks of domestic furnishings.”  

“Our Leelawati project proved timely,” explained Reema Nanavaty, SEWA’s director. “When we first launched it, traditional occupations were being buffeted by globalization, liberalization and other economic changes.  Little did we realize how useful the training would become during the pandemic.”

While the trainings have enabled Muskanben and other crafts persons to broaden their customer base through Facebook and Instagram , most women have used their new skills to weather the pandemic’s disruptions by learning how to carry out basic online transactions.  

Many of them now make cashless payments through PayTm, the BHIM App, and Google Pay rather than meeting people, handling cash and risking infections. 

Mitali Prajapati, whose father runs a utensil shop in Ahmedabad district, remembers the difficulties they faced in the early days of the pandemic. “Our business stalled as my father could no longer travel to other villages to pay his suppliers,” she recalled. “The training helped me overcome my fear of losing money and now I make these payments digitally for him.” Image

“Through this program, our effort has been to open up new livelihood opportunities for poor rural women, promote women-led entrepreneurship and accelerate a national shift towards the greater inclusion of women in the workforce,” said Junaid Ahmad.

Jayshree Gharoda from Gujarat’s Kutch district never used her mobile phone for anything other than calls. Now, this 30-year-old who lives with her husband’s 14-member extended family, pays all the household’s bills online.

Indian Vice President meets President Bio, announces major areas of cooperation

Vice President of India, Shri Venkaiah Naidu, has met President Dr Julius Maada Bio at State House where he announced major areas of support to Sierra Leone that will impact economic development in the immediate future.  

Shri Venkaiah Naidu with President Dr Julius Maada Bio at State House

He praised the government for ongoing economic reforms and disclosed that the agreement with Export–Import Bank of India would, therefore, open a credit line of US$ 30million to support Sierra Leone with a major irrigation development project, boost agricultural productivity at the Tomabom rice project and eventually achieve food self-sufficiency. He encouraged public private partnership and private sector enterprises.  

Sierra Leone’s Vice President Dr Mohamed Juldeh Jalloh and his counterpart said other agreements the two governments had signed were for the establishment of a joint commission, cultural exchange programme and capacity building, which resonated with the President’s flagship human capital development programme.  

Sierra Leone’s Minister of Foreign Affairs, Mrs. Nabeela Tunis, and Director of Telecommunications Consultants India, Mr. Kamendra Kumar, also signed an MoU to participate in the e-VBAB Network Project, a technology upgradation Pan-Africa e-Network venture.

Emphasising the importance of the meeting, Vice President Naidu, who concludes his 3-day visit to Sierra Leone on Monday 14 October as one of only two countries in Africa, said that was the first-ever high-level visit the West Africa nation had had from the Republic of India.

He was accompanied by the country’s Minister of State for Animal Husbandry, Dairy and Fisheries, Shri Sanjeev Kumar Balyan, a Member of Parliament in the upper house of the bicameral Parliament of India, Shri Ramvichar Netam, and senior officers of the Government of India.

President Bio paid tribute to the long-standing relationship between the two countries, citing the role they played as peacekeepers with the United Nations in post-war Sierra Leone. He said the Indian community had also contributed through business to the economy of the country.

“Sierra Leone and India have had a long-standing relationship. Today, as a country, we want to assure the people of India that we will continue to strengthen that relationship for our mutual benefit. Enjoy your stay and thanks for visiting Sierra Leone,” he said.

Creating a More Nutritious Food System with Biofortification

Courtney Meyer, Katrina Boyd, and Jenny Walton

“We want to lead the way to get more nutritious foods on the table.”

The speaker was Arun Baral, chief financial officer of HarvestPlus. His sentiment was shared by the 60 food industry representatives and business leaders who attended the biofortified foods workshop in New Delhi’s Park Hotel.

Following almost ten years of product development and delivery efforts from the HarvestPlus India program, almost half a million Indian farming households were estimated to be growing, consuming, and benefiting from zinc-biofortified wheat and iron-biofortified pearl millet by the end of 2018. In 2018 alone, about 300,000 farming households have been recorded as having procured seeds of these biofortified crops. There are currently nine varieties of iron pearl millet, five of zinc wheat, and one of both iron-zinc sorghum and zinc rice available. Now that crops have been released, attention is turning to exploring opportunities to create a more nutritious food system.

India loses over US$12 billion in GDP annually to vitamin and mineral deficiencies. Biofortification has the potential to become a critical element in the country’s quest for Kuposhan Mukt Bharat (Malnutrition Free India) by 2022; last year the Indian Council for Agricultural Research set minimum levels of iron and zinc for pearl millet varieties—signaling nutrition as a priority for breeders.

But ending hidden hunger and managing a profitable food business can be done simultaneously and sustainably. By addressing the barriers to embedding biofortification into the food system, HarvestPlus aims to increase the access families and communities have to nutritious seeds and foods.

“We will increase the number of farmers in India growing and consuming zinc rice, zinc wheat, and iron pearl millet by creating a market for these foods,” said Wolf Pfeiffer, director of research and development at HarvestPlus.

Following the success of similar food industry workshops, attendees convened with the aim of bringing biofortified food products to more Indian consumers by identifying sustainable routes to market. The goal was to overcome barriers and identify opportunities such as ensuring supply chain integrity and meeting manufacturing standards.

Speakers and attendees spanned the supply chain, from agricultural researchers, seed producers and sellers, farmers, aggregators, millers and food manufacturers, to marketers, consumer researchers, advertisers, communicators, and advocates. Discussions were designed to determine how to best address potential barriers and identify motivating factors that will engage and intrigue consumers and businesses. Participants committed to finding solutions and partners to address bottlenecks in the supply chain.

“As farmers we are proud to be actively involved with the HarvestPlus program since its inception…in testing new zinc wheat varieties, and seed production. Now we are planning to establish a flour mill,” said attendee and partnering farmer Harbansh Singh.

The pioneer of biofortification, HarvestPlus continues to share knowledge and facilitate connections among the growing network of partners to drive and connect supply and demand.

“Let’s work together for a nutrition revolution,” said keynote speaker and chef Ranveer Brar.

Who am I? A reflection on my participation in the Kumbh Mehla 2019

By Ahmed Sahid Nasralla (De Monk)

De Monk

My early memories, or rather perceptions, of India were entirely influenced by Bollywood movies. I actually fell in love with India when I was in secondary school in the late 80s and early 90s, through popular movies such as Sholay, Ghazaab, Yaadonki Baraat, Love Story, Disco Dancer, Yeh Vadaah Raha, Nagin (The Snake Girl), The Burning Training and actors such as Dhamendra, Amitabh Bachan, Jeetendra, Amjad Khan, Ranjeet, Mithun Chakraborty, Govinda, Amrish Puri, Hema Malini, Rekha, Rena Roy, Zenat Arman and many more.

I would skip classes at St. Edward’s Secondary School at Kingtom, Freetown to watch matinee at Globe Cinema on Syke Street. On some weekends I would sell my day’s meal and use the money to buy tickets into Starco Cinema on Kissy Road/Savage Square. Other times, our uncle who used to manage the bar and restaurant at Strand Cinema on Waterloo Street, would give us matinee tickets and we would spend the whole weekends watching Indian movies. At some point I even kept a small book where I listed all Indian movies I watched, and they were running into a thousand or more.

The images of India I formed during that period were a nation that communicates well through their unique culture and tradition of singing and dancing for every occasion and worshipers of idols as symbolized by the deity Krishna and other objects such as trees, mostly shown in their movies. And then the popular Hollywood movie featuring Anil Kapoor, ‘Who wants to be a millionaire?’ in recent times, gave me another perspective of India all-together- a nation caught between the cities of paradise and the slums of the earth.

However, as Euro-Western influences begun to show strongly in Indian movies due probably to the influx of the new generation of actors born and raised in Europe and the US into Bollywood, my interest diminished gradually. Nonetheless, the nostalgia for the old movies is still there as once in a while I would sneak into YouTube and watched my old favourites, and the memories of the cinema- which just vanished one morning in my country- would come back.

So when I got the invitation from the Government and People of India through their Ministry of External Affairs and the Indian Council for Cultural Relations (ICCR) to attend the Kumbh Mehla 2019, I felt excited about the prospect of stepping on Indian soil. Moreover, the prospect of having lunch and a group photo with Prime Minister Narendra Modi makes it all the more enticing.

The Kumbh (meaning confluence or gathering) is undeniably the largest human gathering where people from all walks of life across the world come to partake and experience India’s age-old culture and tradition which celebrate diversity and promote peace and unity. For the one month (February-March 2019) cultural and spiritual festival, the Kumbh hosts more than 230 million people of all socio-political stratifications.

And there I was, at the Lemon Tree Hotel in Delhi on the morning of 21 February, 2019, joining other delegates from around 186 countries across the world. So right there at the hotel the Kumbh started, with delegates trying to acquaint with one another and learning about each other’s country and culture. You can learn about nations, their people and culture on the Internet, but to hear all of it and even more from the citizens themselves is quite a different enlightenment all-together.

Similarly, of course, enough has been documented by the Ministry of External Relations and the ICCR in the forms of brochures, flyers, posters, banners, photos, books, video documentaries and films but nothing compared to witnessing and experiencing the Kumbh personally. The experience of feasting on a panoramic view of the breathtaking landscape hosting the Kumbh pilgrims dotted with stretches of tents, canoes mobile and wash rooms; the experience of seeing firsthand the good, bad and ugly of the second most populated nation on earth; the experience of embracing the sacred fig tree (Ashayvat) and kissing it many times in an effort to get a piece of its immortality; the experience of the breathtaking site of Sangam Nose, the confluence of river Ganga, Yamuna and the mystical river Saraswati; the experience of appreciating and respecting every living thing as an important creation of God; the experience of witnessing the pleasant but strict security alertness of the Indian Police…

My climax is not the meeting with Prime Minister Modi, but the experience of taking a holy dip at the sacred waters of the river Ganga. Though hesitant at first, I find myself voluntarily and gently stepping into the mystical waters and taking a long purposeful dip. Stepping out of the water after a bath, the feeling was refreshing. I felt some kind of inner peace and control, and a strange sense of selflessness. And the life-long question dawned on me: who am I actually? In the midst of such diversity and a very strong connection to mother Nature as displayed at the Kumbh, I realized I was not as important as my ego had led me to believe all this while. I realized that my importance as a person is just as important as the importance of any other living thing- from the smallest of ants to the gigantic fig tree or the highest of mountains- to the existence of the Universe. I felt the renewal of my mind and the broadening of my horizons to include all things I once looked low upon or taken for granted. To live a life of fulfillment is to live not for the self but for the general good of all living things, including the environment.

So I take away with me a new impression of India- a nation proud of the diversity of its culture, tradition and people; a nation with an open heart- ready to learn and share their experiences to the rest of the world; a nation that believes in democracy in every aspect of its national life; a nation with a deep sense of belief in the purpose of this life: service unto others.

My only disappointment was not seeing or meeting the famous Indian actors during the Kumbh. With a program as unique and important as the Kumbh heritage, what better ambassadors can this nation get other than the popular Bollywood actors who had long forged (and continue to) a connection between the great nation of India and the rest of the world?

Namaste.    

Note: The author is a journalist from Sierra Leone and was with the Saraswati group during Kumbh Mehla 2019.