A recombinant option for flu pandemic – Deccan Herald

A recombinant option for flu pandemicThe inevitability of a future flu pandemic is a grim reality, exacerbated by increasing globalisation, global warming, urbanisation, and mobility.

Last Updated 19 November 2023, 03:48 IST

In 2018, the world marked the centenary of the devastating1918-19 influenza pandemic, which claimed over fifty millionlives. Today, as we grapple with the aftermath of the Covid-19 pandemic, the World Health Organisation (WHO) issues stark warnings about the looming threat of another influenzapandemic. Recent history bears witness to influenza pandemics in 1957-58, 1968-69, and 2009-2010. The inevitability of a future flupandemic is a grim reality, exacerbated by increasingglobalisation, global warming, urbanisation, and mobility.

These pandemics stem from the influenza virus capacity toinfect multiple species and occasionally recombine, creatingnew infectious strains to which humans have little immunity.

ADVERTISEMENT

Heightened concerns about potential human-to-humantransmission arise from increasing H5N1 avian-origininfluenza cases among mammals, (biologically closer tohumans than birds).Influenza pandemic in the future is a real risk, when is the big question, says Dr Sylvie Briand Director of the Pandemicand Epidemic Diseases Department at the World HealthOrganisation.

Influenza viruses have circulated for centuries, causing severe illnesses, particularly among children, the elderly, pregnantwomen, and those with underlying health conditions.Globally, influenza results in an estimated one billion human cases and 2,90,000 to 6,50,000 annual fatalities.

To combat the threat of influenza, Professor RaghavanVaradarajan of the Molecular Biophysics Unit at the Indian Institute of Science (IISc) collaborates with Dr GauthamNadig as co-founders of Mynvax. Together, they aredeveloping recombinant vaccines with improved efficacycompared to current vaccines and enhanced breadth ofprotection.

Since 1973, the World Health Organisations Global InfluenzaSurveillance and Response System (GISRS) has defined thecomposition of the seasonal influenza vaccines. Expertconsultations occur biannually in February and September for the Northern and Southern hemispheres respectively, leadingto annual vaccine updates.

When is flu season?

The Indian Council for Medical Research (ICMR) NationalInstitute of Virology (NIV) in Pune, a WHO-designatednational influenza centre, has diligently monitored influenzaand other respiratory infections since 2004. NIV has identified two distinct peaks of influenza activity: one during monsoon(June-September) and another during winter (November-January). Dr Varsha Potdar, Influenza group leader at NIV,reveals that despite Indias northern hemisphere location, cities with temperate seasonality benefit from vaccinations inSeptember-October, while cities experiencing flu peaks duringthe monsoon season, benefit from April-May vaccinations.Traditional flu vaccines rely on an egg-based manufacturing process, used for both inactivated (killed) vaccines (flushots) and live attenuated vaccines (the nasal spray flu vaccine). However, inactivated vaccines developed duringthe Covid pandemic did not stimulate a robust immunogenicresponse. These vaccines lack the virus-killing potentialmediated through a type of white blood cell called TLymphocytes, according to Dr Satyajit Rath, an immunology expert and emeritus professor at the Indian Institute ofScience Education and Research (IISER) in Pune. Professor Jeffrey Almond, a vaccine expert from Oxford,notes that current flu vaccines offer limited protection (around50-60%), contrasting with vaccines for diseases like mumpsand measles, which boast of efficacy rates around 90%. Thislower efficacy contributes to lower vaccine uptake in manycommunities.

Egg-based vaccines, while reliable, face challenges due to themassive quantities of hen eggs required, and this could getmore challenging considering climate change, fears DrShahid Jameel, a noted virologist. Cell culture vaccines, theother vaccine platform, are expensive. Thus, developing arecombinant vaccine based on a single protein that can bescaled up during a pandemic is worth pursuing, pending efficacy studies. Explaining the technology behind their recombinant vaccinedevelopment, Dr Nadig and Prof Varadarajan elaborate thatthey first obtained the virus gene containing the geneticinstructions for making HA (Haemagglutinins). HA is anantigen, a feature of the flu virus, which triggers the humanimmune system to create antibodies that specifically target thevirus.

The HA gene is combined into a baculovirus, a type of virusthat infects invertebrates. This HA-containing baculovirus isused to infect a particular type of insect cell line where itrapidly produces HA antigens in bulk, collected, and purified.

Thus, baculovirus is only used to deliver genetic instructions for making HA antigens in the cell, and the vaccine does notcontain any virus in it.

Dr Satyajit Rath commends Mynvaxs earlier success increating a temperature-stable Covid-19 vaccine formulation,now applied to influenza. A stable vaccine at extremetemperatures would be invaluable from an Indian perspective, states Dr Jameel.

Extensive analysis of 75 years of virus sequences from thedatabase has led to the design of a conserved HA region.Coupled with strategies to enhance antigen yield and the useof an adjuvant (an ingredient used in vaccines to increase the response), this development is expected to result in a moreeffective vaccine.

The developers of the Mynvax vaccine are optimistic about itspotential. Animal studies have demonstrated protectionagainst diverse viruses dating back to 1934. Moreover, therecombinant vaccine overcomes limitations associated with relying on hen eggs, which could face shortages during a pandemic, and with the virus undergoing adaptation in the eggpotentially reducing vaccine efficacy. Phase 1 trials arescheduled to commence in Australia later this year, with phase 2 and 3 trials planned in India for the following year. While a universal influenza vaccine remains a distant goal,achieving an average protective efficacy of about 70-80% against seasonal influenza would be a significantachievement, says Prof Varadarajan.

Prof Almond envisions that a more effective vaccine could boost vaccine production and uptake several billion dosesseasonally, with a market reach of up to 30 to 40 billiondollars, potentially benefiting lower-income countrieseventually.

(The author is a consultant haemato-oncologist with aspecial interest in stem cell transplantation at RoyalWolverhampton NHS Trust, UK. He can be reached at praveen.kaudlay1@nhs.net)

See the original post:

A recombinant option for flu pandemic - Deccan Herald