Coronavirus Vaccines: Mirror, mirror on the wall, who's the fairest of them all?

Children, younger people and some other categories of persons will have to possibly wait till 2022 to get vaccinated.


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This tricky pandemic called COVID-19 has been ravaging humankind for nearly one full year now. And, the global scientific community has been relentlessly on the hunt for a Covid vaccine for about nine months now. Till a few weeks ago, we were fervently praying for just a safe and effective vaccine, just a single one, if not more! Today, we have a handful of vaccines that already touched the finishing line or are fast closing into it.

We have three vaccines well ahead of many other promising candidates (leaving aside the Chinese and Russian vaccines for the time being): Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca vaccines. Initially, the Oxford vaccine seemed to be ahead in the race but Pfizer vaccine has beaten it in the intensely competitive race.

Pfizer had released full late-stage trial data on November 28, 2020 following which the UK granted emergency use authorization (EUA) of its vaccine on December 3. Canada followed suit by granting approval on December 9. The US also green lighted this vaccine on December 11, 2020. It's learnt that a few other countries including Bahrain and Mexico have also approved emergency use of the Pfizer vaccine.

The Pfizer vaccine has taken an amazingly short time of just nine months from initial studies to approval. The world's record of the fastest vaccine so far was the mumps vaccine that took just four years of development from the Lab to the Clinic. From no vaccine just a while ago, now we are in the enviable position of weighing the pros and cons of a handful of vaccines closing toward the finish line now!

Pfizer Vaccine: Pros and Cons

 The Pfizer vaccine data involving more than 43,000 volunteers have been peer-reviewed and published (New England Journal of Medicine [NEJM], Dec. 10, 2020) and it was found to be 95 per cent effective in preventing disease symptoms, when tested one week after participants were given their 2nd shot of the vaccine. The vaccine didn't reportedly cause any serious adverse side effects.

However, scientists warn that the vaccine must still be subject to long-term surveillance about any possible concerning issues that may arise. First, we need to establish if the vaccine just prevents disease symptoms or it also prevents transmission of SARS-CoV-2 coronavirus. It's quite possible that some vaccinated individuals may be susceptible to asymptomatic infections and, though they themselves may be fine, they may shed the virus everywhere and transmit it unwittingly to many other people. Second, we're still not sure about the long-term side effects of the vaccine. Six people reportedly died during the Pfizer phase-3 trial. The vaccine's side effects were mostly mild: fever, headache and fatigue but four people developed Bell's palsy (weakening of some face muscles) during the trial. Two persons suffered allergic reactions (anaphylaxis) on the first day of vaccination in the UK (Nature, December 11, 2020). Third, we need to ascertain the longevity of the immunity elicited by the vaccine, whether it's months or years, by monitoring the level of antibodies and immune cells in the blood of vaccinated individuals (Nature, December 10, 2020). Fourth, there's the need to ascertain if the vaccine works in older people, pregnant women, and young children. Fifth, we need to be vigilant about the possibility of SARS-CoV-2 virus evolving (mutating) to escape the immunity conferred by Pfizer or other vaccines.

Another worrisome issue is that the Pfizer trial lacks data about Asians. Only 4.3 per cent of phase-3 trial participants were Asians and the efficacy on this group was only 74.4 per cent, whereas the overall efficacy was calculated to be 95 per cent for the consolidated trial population comprising 83 per cent Whites (The Mint, December 11, 2020).

Pfizer and other close runners

Two other vaccines are following close on the heels of the Pfizer vaccine: Moderna and AstraZeneca vaccines. Let's compare these 3 vaccine candidates in terms of cost, distribution, storage, efficacy and approval.

Both Pfizer and Moderna vaccines are mRNA or genetic vaccines and are highly unstable at room temperature and must be kept frozen at ultra-cold temperatures. The AstraZeneca vaccine uses the viral vector platform and is relatively much more robust and can be stored at refrigerator conditions (2-80C). All three vaccines require 2 shots given about 3-4 weeks apart. In terms of cost, the Oxford vaccine is the best for low-income countries. Its cost of just $4 (approx. Rs 300) per dose is much more affordable than the Pfizer vaccine ($20, about Rs 1,500) or Moderna vaccine (S15-25, about Rs 1,100 to 1,900) per dose.

In terms of storage, the Pfizer vaccine seems the most challenging. It requires -700C (colder than Antarctica) for long-term storage and dry ice packaging for shorter storage and transport. Moderna vaccine needs to be stored at -200C, whereas the Oxford vaccine remains stable for long at just 2-80C. The AstraZeneca vaccine also seems more attractive in terms of equitable distribution across the globe, as it's part of the WHO-supported COVAX facility that aims to give vaccine access to low-income nations (about 70-80 per cent of Pfizer and Moderna vaccine doses have been already pre-ordered by just a few rich countries).

In terms of efficacy, both Pfizer (95 per cent) and Moderna (94.1 per cent) vaccines look very promising. But the data about Oxford vaccine seems a bit problematic. The late-stage trial data for the AstraZeneca vaccine has now been published (Lancet, December 8, 2020). The overall efficiency of this vaccine is estimated to be about 62 per cent with two full doses, given four weeks apart but 90 per cent if the vaccine is administered in a half dose (1st shot) followed by a full dose, a month later. It's still perplexing how to calculate the actual efficacy of the Oxford vaccine.

However, both Moderna and Oxford vaccines are expected to apply for EUA shortly. We may hope that these two vaccines may be granted emergency use approval by late December 2020 or early January 2021. We need to be particularly hopeful for the AstraZeneca vaccine as it seems much more suited to the Indian conditions.

Some other players

Several other players are also in the running for the COVID-19 vaccine. Novavax vaccine (storage in refrigerator conditions, two doses three weeks apart) is still in late-stage trials but may be expected to be approved in the first half of 2021. An Innovio vaccine (needle-free vaccine delivery, room temperature storage,  two doses, given four weeks apart) may be quite attractive for elders and children. It's in mid-stage clinical trials and can be expected for release in summer of 2021.

Indian vaccine scenario

Though India is trying to fast-track review of the Pfizer vaccine for use in our country, it's not much suitable for Indian conditions as I have explained before. What then are the possible vaccine candidates vying for emergency use approval or full approval in India? Three candidates recently approached DGCI, Govt. of India requesting EUA: Pfizer, CoviShield (SII, Indian version of Oxford vaccine), and Covaxin (weakened coronavirus vaccine, BBIL, indigenous vaccine). Though the government is still reviewing the Pfizer vaccine, it has put on hold approval of both the Serum Institute and Bharat Biotech vaccines, citing lack of sufficient data.

Covaxin is in phase three trials currently, so also is the CoviShield. ZyCoV-D (2 versions, one DNA vaccine and the other made using live measles virus platform), vaccine made by Zydus Cadila, began its phase-2 trials in August 2020 (Jagran English, December 8, 2020). Biological E and Mynvax (protein subunit vaccine, can be stored at room temp. for more than a month) vaccines are now in Phase 1/2 trials.

Recently, the government has green lighted the start of clinical trials for Indian mRNA vaccine made by Gennova Pharmaceuticals. The Indian vaccine taskforce plans to vaccinate about 30 crore (300 million) Indians by August 2021. This will require 60 crore vaccine doses (of the same vaccine or a mix of vaccines that will soon get approved). Of these about 1 crore will be healthcare workers (doctors/nurses etc.), 2 crore of other frontline workers (police and other essential service staff) and the remaining will cater to people aged 50 or above and those below age 50 but with co-morbidities. Children, younger people and some other categories of persons will have to possibly wait till 2022 to get vaccinated.

So, in the meantime, we must not let our guards down and we must still strictly observe the non-pharmaceutical interventions such as the major SOPs of the use of face masks, physical distancing, and hand hygiene and avoidance of 3 Cs: crowded places, close contact settings, and closed spaces (with poor ventilation).

Coda

The silver bullet for Covid-19 is an efficacious, safe, and affordable vaccine and/or drug. But we don't have it yet. But as Derek Thompson writes in The Atlantic magazine (October 12, 2020), there are "bronze bullets abound." The 3 Ws (watch your distance, wear a mask, and wash your hands regularly) and 3 Cs (avoidance of crowded places, closed contact settings, and closed spaces) are some of these bronze bullets. At this critical point of the pandemic, it's we-hoi polloi, common people-who with our (in)appropriate behaviour will determine the trajectory of Covid-19 in Manipur. Once again I humbly appeal to fellow citizens to abide by the 3 Ws and 3 Cs guidelines strictly!

In addition, the public health authorities may consider a few things, if feasible: localized, focused lockdowns in specific areas, mass testing at containment zones and hotspots of infections, rapid contact tracing and isolation/quarantining of potentially infected cases/sick patients, weekly publications of Covid graphs with categories of infected people and mortalities, strengthening of healthcare facilities, timely palliative/supportive care and treatment of serious Covid (and non-Covid) cases, and clear and accurate messaging from a designated public health official (just one designated person) on a regular basis (say weekly, if not daily).

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First Published:Dec. 13, 2020, 8:02 p.m.

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