This new pandemic called Covid-19 has ravaged nearly all countries of the world and yet this alarming global scourge is still not showing any signs of slowing down. As of this writing, there are about 32.8 million cases of infections globally, with over 9.9 lakh deaths. India is the second worst affected country, with more than 59 lakh (5.9 million) cases of infection, and over 93,000 deaths. The situation in our country is quite alarming as daily rises have been in the range of 70,000 to nearly 1 lakh cases for the past several days!
Manipur's situation is not yet alarming but there is also no room for complacency. The government is taking all possible steps, I believe, to contain the disease. However, if the public doesn't strictly abide by the recommended control and preventive measures such as use of masks, social distancing, hand hygiene, regular use of soaps and hand sanitizers and religious maintenance of quarantine/isolation SOPs, the outbreak may go out of control! Till date, the number of cases in Manipur have shot up to 9,791 cases with 7,365 recoveries, and 2426 active cases and the number of deaths stand currently at 63.
There is currently no approved drug or vaccine for Covid-19. Several vaccine candidates are in late-stage trials. Besides the promising drugs, dexamethasone and remdesivir, there is currently a novel class of treatments called monoclonal antibodies (mABs). Regeneron, Eli Lilly, Abcellera and other pharmaceutical companies are currently conducting trails for single mAb candidates or mAb cocktails.
A safe, effective, and affordable vaccine in wide usage may only be available by the middle of 2021 only. Meanwhile, we have to strictly adhere to standard prevention and control procedures such as use of masks, hand hygiene and physical distancing. A faint glimmer of hope may come in the form of an effective and safe monoclonal antibody, much earlier than the first vaccine. That's why we call the mAb as 'the bridge to a vaccine.' We shall discuss details of mABs in future columns.
In today's column, I would like to review the status of Covid-19 vaccines. Clearly, the frontrunners are candidates made by AstraZeneca, Moderna, and Pfizer. A few late-bloomer vaccine candidates have recently caught up with the race. One such candidate is the vaccine being developed by Janssen, a subsidiary of the pharmaceutical giant, Johnson & Johnson (J&J).
What's the J&J Vaccine?
This vaccine is prepared using the non-replicating viral vector platform, just like the vaccine being developed by the University of Oxford in coordination with AstraZeneca Inc. Both the Moderna and the Pfizer vaccines are made using the mRNA vaccine platform (a as-yet untried platform). The Janssen vaccine is technically called JNJ-78436735. This vaccine is also known as Ad26.COV2.S.
What is Ad26.COV2.S?
Ad26 is human adenovirus serotype 26 causing common cold. This adenovirus acts as the vector (carrier) of the genetic information of the SARS-CoV-2 coronavirus. It's thus a recombinant virus vaccine. The adenovirus genetic molecule has been engineered to carry the genetic information for the coronavirus spike protein, S.
The adenovirus has been inactivated so that it doesn't replicate inside the human body and thus unable to cause common cold in humans. It is used to deliver the spike protein genetic information inside human cells. Once the vaccine enters the human body, the coronavirus spike protein is expressed and it trains the body's immune system to recognize SARS-CoV-2 (the coronavirus causing Covid-19) and elicit an immune system against the coronavirus thus protecting vaccinated individuals from Covid-19 when they encounter the coronavirus.
J&J Vaccine Protects Monkeys Against SARS-CoV-2
In a peer-reviewed paper published in the premier science journal Nature on July 30, 2020 [Nature https://doi.org/10.1038/s41586-020-2607-z (2020)], it was clearly shown that the vaccine protects monkeys against SARS-CoV-2 coronavirus after receiving a single shot of the Janssen vaccine. 32 monkeys were given injections of the experimental vaccine, while 20 animals received placebo (for example, a physiological saline solution).
All vaccinated animals developed neutralizing antibodies against SARS-CoV-2, the coronavirus that causes Covid-19, of which 6 who got optimal doses of the vaccine didn't show lung infections, after being exposed to the virus. The 20 animals that received fake (sham) shots all became sick with Covid-19-like symptoms. However, protecting monkeys is still a far cry from protecting humans against the cornavirus.
Phase 1/2 trial results
Subsequently, a combined phase 1/2 (early to mid-stage) trials of Ad26.COV2.S vaccine was conducted in about 1,000 healthy individuals in US and Belgium. The results were found to be very promising.
The trial data have now been published as a preprint at the preprint server, medRxiv, on Sep. 25, 2020 (doi: https://doi.org/10.1101/2020.09.23.20199604).
A single shot of the J&J vaccine produced a strong immune response against the novel coronavirus. The vaccine was well-tolerated at two different doses (lower and higher doses). However, it wasn't clear whether elderly people will be protected to the same degree by this vaccine as younger individuals. 98% of volunteers had neutralizing antibodies, that defend human cells from SARS-CoV-2, 29 days after vaccination.
In volunteers older than 65, the adverse side-effects such as fatigue and muscle aches was 36%, much lower than 64% seen in younger participants. This showed that the immune response in older people may not be as robust as that in younger individuals. The early-stage data indicated the vaccine's suitability to be tested for large-scale safety and efficacy data in a phase 3 trial with thousands of volunteers.
Ad26.COV.S vaccine enters Phase 3 trials
J&J has initiated late-stage (Phase 3) trials on Sep. 23, 2020. It's the most ambitious of the late-stage trials among 9-10 candidates that have reached phase 3 trials. It's an advanced, large-scale, multi-country trial of the candidate JNJ-78436735. This large-scale trial has been code-named ENSEMBLE trial and plans to enroll almost 60,000 volunteers across 3 continents and involving 215 sites in Argentina, Brazil, Chile, Columbia, Mexico, Peru, South Africa and the US.
The late-stage trails will study the safety and efficacy of the vaccine in a heterogeneous population of varied age groups, ethnicity, and health conditions. It would study if the vaccine can prevent Covid-19 infections in vaccinated individuals as compared to those receiving placebo shots in people of age 18 years and older, including those over age 60 and including people with co-morbid conditions.
The phase 3 results are expected to be ready by the end of 2020 or early 2021. This is because vaccinated individuals and those getting placebo shots will have to be monitored for several months to get a chance of exposure to the virus and see if the vaccine protects individuals from Covid-19. Moreover, thousands of volunteers across the globe have to be carefully studied for several weeks to see if any of them develop rare adverse events due to the vaccine (as was seen recently in the case of the Oxford vaccine, with one volunteer developing a rare spinal cord inflammation).
Can the phase 3 trial time be shortened?
Human challenge trials
There is a controversial method called human challenge trial. In this approach, the vaccinated individuals are deliberately infected with the virus; in this case, SARS-CoV-2, to study if the vaccine can protect them from the viral disease; in this case, Covid-19. However, it's debatable if it's advisable to deliberately infect healthy people with a novel virus for which we have neither a cure or a vaccine yet.
However, a challenge trial for the Oxford vaccine is being planned to be carried out in about 100 individuals in London in January 2021; to be kept in a safely quarantined facility away from the general population!
Advantages of the J&J vaccine
There seem to be several advantages of the Janssen vaccine over the rival candidates. First, it's a single-shot vaccine and so would be easier for manufacturing and distribution (for example, to vaccinate 100 million people, we would need 200 million doses of Moderna/Pfizer/Oxford vaccine, whereas we would need just 100 million doses of the J&J vaccine. Second, it's a tried-and-tested platform that has shown success with many earlier vaccines e.g. Ebola, RSV and Zika vaccines. Fourth, J&J has a large manufacturing capacity and it aims to make and distribute about 1 billion doses of the vaccine in 2021 alone. Last, the J&J vaccine is more stable and can be kept in refrigerator in liquid form for up to 3 months before use, whereas the Moderna and Pfizer vaccines are much more unstable and needs to be kept frozen or at ultracold temperatures until shortly before use.
In addition, being a late-bloomer, the Janssen vaccine has got time and opportunity to learn from the mistakes of its predecessors, i.e. AstraZeneca, Moderna, and Pfizer vaccines.
There is as yet no approved cure or vaccine for COVID-19. Meanwhile, it's likely that the number of morbidities and mortalities would continue to soar across most parts of the world including India (and Manipur). What then should we do meanwhile before the development of an approved cure or vaccine.
The government must strictly enforce the standard SOPs for tracing, testing, and treating potential infection cases. Within the limits of the available budget, testing must be scaled up to catch more of potential infections including asymptomatic cases. If feasible, antibody based screening (serosurveillance) may be done in infection hotspots to monitor the spread of the infection and percentage of population who has developed immunity against the Covid-19 virus.
Three kinds of hospitals or treatment facilities need to be set up: first, to treat critical Covid patients; second, to address non-Covid cases, and third, to manage long Covid 'recovered' individuals.
The general public must also religiously abide by the necessary control and prevention measures (use of masks, social distancing & hand hygiene etc.); we need to be a tad altruistic: please remember that you're sacrificing a little bit of your creature comforts not just to save your own life but also others' lives!
(The views expressed are personal)
