Top 3+1 COVID-19 vaccines: Which one will smash the finish line?

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A volunteer receives a shot in the first-stage safety study clinical trial of a potential vaccine for COVID-19, the disease caused by the new coronavirus, at the Kaiser Permanente Washington Health Research Institute in Seattle.
Image Credit: AP

Highlights

  • There are currently 16 leading vaccines listed by the WHO
  • We profiled the top 3, based on their trial milestones, plus one possible dark horse
  • What each vaccine trial needs to achieve to win the race

DUBAI: The world is on tenterhooks. A coronavirus vaccine is one of the most-awaited events of 2020-21.

But what if the virus just goes away, vanishes like the first SARS, never to be seen again?

The best minds, big pharma and big powers are accelerating time-critical research. Thousands of scientists and thousands more trial participants are involved in this multi-billion-dollar global enterprise.

It’s an ambitious, unprecedented endeavor going at “warp” speeds.

Now, the vaccine race is about to smash the finish line, keeping everyone on pins and needles.

3+1 leading candidates

At the moment, three leading vaccines are getting the most attention:

(1) UK’sOxford-AstraZeneca vaccine;

(2) US Moderna-NIAID mRNA vaccine; and

(3) China’s CanSino Biologics’ adenovirus-based recombinant vaccine.

A potential dark-horse:

(4) Sinopharm China National Biotec Group’s (CNBG) vaccine, the first COVID-19 inactivated vaccine to enter the final (Phase III) trial, in collaboration with Department of Health Abu Dhabi. 

Phase III trial 001
Image Credit: Gulf News

Time, timing

Time, or timing, is everything. It can happen so fast, or a bit later. Now, restrictions had been lifted, but we’re still on our guard. But new mini-outbreaks have riled markets, and fanned talks of a “second wave”.

There are many unknowns. Or maybe there’s no finish line.

In SARS-CoV-2’s deadly run, the jury is still out, especially on the question of the real infection fatality rate (death against infections). At best, data scientists can only guess, as it’s dicey to pin down the number while a pandemic remains active.

But we do need a jab that works and is safe.

Here, we list the top front-runners (Phase II and Phase III trials), based on the latest publicly available WHO data (as of June 24, 2020). 

1. Oxford-AstraZeneca

The University of Oxford’s Jenner Institute and AstraZeneca Plc.’s experimental vaccine was among the first to enter the final stages of clinical trials. Their ChAdOx1 nCoV-19 candidate is based on adenovirus. Jenner Institute is spearheading this research.

The institute, formed in November 2005 through a partnership between the University of Oxford and the British government, is named after Edward Jenner, a British physician who is deemed the father of immunology, credited for developing the smallpox vaccine in 1796. Funding for Oxford’s COVID-19 vaccine research comes from governments ($1.2 billion grant from Washington), corporations, trusts, foundations and philanthropic donations.

2. Modern’s mRNA vaccine

Name of Vaccine: mRNA-1273

Currently, the most advanced vaccine development method is the mRNA (messenger ribonucleic acid). It hold much promise, but this relatively new platform remains unproven. If it does deliver, it is hoped to speed up — “revolutionise” — vaccine development.

The mRNA technology used by Moderna relies on the body’s own cells to produce viral proteins. Within the bigger, several mini-trials are being conducted, for example, involving different doses: 50 mcg on adults aged 18-54 years; 50 mcg on the 55+ age group; 100 mcg on adults aged 18-54 years and 100 mcg on +55 age group.

Moderna recently said its mRNA-1273 elicited neutralising antibodies in subjects “at or above” convalescent serum from people who had recovered from COVID-19.

3. Cansino Biologics

Name of Vaccine: Ad5 nCoV

This jab uses an adenovirus as a vector to carry the genetic information of the SARS-CoV-2 spike protein to trigger an immune response. Phase 1 trial results were published on May 22, 2020 in the peer-reviewed medical journal The Lancet.

The results show Ad5 nCoV, funded by China’s National Key R&D Program, National Science and Technology Major Project, and CanSino Biologic (listed on the clinicialtrials.gov database) induced binding antibodies in most of the patients within 28 days — and appeared to be “safe and well-tolerated” by 108 healthy volunteers ages 18 and above age.

4. Sinopharm

Name of vaccine: BBIBP-CorV

BBIBP-CorV of Sinopharm is made from an inactivated form of the SARS-CoV-2 virus. On June 6, 2020, team of Chinese researchers reported in the journal Cell that it induced high levels of neutralising antibodies against SARS-CoV-2, in rhesus macaques without triggering any serious adverse events.

On June 23, 2020 the UAE announced the world’s first Phase III clinical trial of a COVID-19 vaccine candidate.

Beijing-based pharmaceutical giant Sinopharm China National Biotec Group (CNBG) signed a clinical trial agreement with Group 42 (G42), the Abu Dhabi-based leading AI and cloud computing company. G42 will lead the clinical trial operations in the UAE under the supervision of the Department of Health of Abu Dhabi.

It’s not immediately clear if BBIBP-CorV is the vaccine that will undergo Phase III trial in Abu Dhabi.

Q: What does it take for vaccine candidates to “win”?

It takes time, and lots of healthy volunteers for the trials. More specificially, the studies are “randomised, double-blind, placebo parallel-controlled trials”.

The trials evaluate the safety and “immunogenicity” of the vaccine candidates in healthy populations, usually targeting specific age groups.

IMMUNITY, IMMUNIGENICITY

IMMUNITY — the ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells.

IMMUNIGENICITY — The ability of a foreign substance, such as an antigen/antivirus, to provoke an immune response in the body of a human or other animal; in short, the ability to induce a humoral (relating to body fluids) and/or cell-mediated immune responses.

In Phase III in particular, participants are randomly allocated to receive the investigational vaccine or a placebo vaccine.

Volunteers will be followed up for several months (at least 12 months), and they will be tested for COVID-19 if they develop any symptoms which may represent the disease.

Moreover, blood tests will be done during the study to look at how the volunteers’ immune systems have reacted to the virus.

At the end of the study, the researchers will look at how many people had COVID-19 disease in each group and this will help them to decide if the vaccine has worked.

GLOSSARY

Randomised trial — people are allocated at random (by chance alone) to receive one of several clinical interventions.

Double-blind trial — neither the participants nor the researcher knows which treatment or intervention participants are receiving until the clinical trial is over. This makes results of the study less likely to be biased.

Placebo-controlled studies — a way of testing a drug or therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate “control” group receives a sham “placebo” treatment which is specifically designed to have no real effect.

At the end of the study, the researchers will look at how many people had COVID-19 disease in each group and this will help them to decide if the vaccine has worked.

Q: What’s different this time? What happens after a winner — or winners — come out?

The big difference this time is the massive collaboration among the scientific community and an almost instantaneous sharing/scrutiny of data. There’s been promises of an early release of a vaccine, and making it “affordable.”

Once approved, the vaccine will go into mass production.

Experts say billions of doses may be needed to be produced. Lots of collaboration need to be coordinated to pull this off between the scientists, manufacturers, governments and people involved in logistics.

Distribution to all corners of the world will be a challenge, but necessary to achieve the desired level of immunity.

“The first country to the finish line will be first to restore its economy and global influence,” former FDA commissioner Scott Gottlieb wrote in The Wall Street Journal.

Q: Where can we find the list of vaccine candidates?

The World Health Organization (WHO) keeps a list of candidates in “landscape documents” for information purposes (download the attached pdf file):

Disclaimer: The WHO states that inclusion of any particular product or entity in any of these documents does not constitute, and shall not be deemed or construed as, any approval or endorsement by WHO of such product or entity (or any of its businesses or activities).

Translation: It’s just a list. The safety and scientific validity of studies/trials on the list is the responsibility of the study sponsor and investigators. There’s no endorsement of the validity of trials from any health authority at the moment.

Moreover, the WHO does not guarantee the accuracy of the information on thes landscape documents. If researchers fumble or play around with data to pass trials, the WHO cannot be held responsible or liable.

Q: What do scientists need to show before a jab is seen to work?

Vaccine development is a long process. In general, there are 3 phases:

Phase I

After evaluation in test tubes and animals, a vaccine is tested in humans in Phase I trial. This is a small study that assesses safety and immune response to gauge its potential.

Phase II

Scientists find the optimal dosing and further understand a vaccine’s safety and immunogenicity in more healthy subjects. Given the urgency of a global pandemic, many are compressing the two phases (Phases I & II) into a continuous trial design.

Phase III

Thousands of healthy people given one or several doses of the vaccine (+ pain/fever medication given within first 24 hours after receiving vaccine).

Participants will be evaluated over 12-month period (follow-up visits at day 28, 90, 182 and 364). people with virologically confirmed (PCR positive) symptomatic cases of COVID-19 over the course of 12 months.

Phase III Phase 3 002
Image Credit: Gulf News

Challenges

In the massive Phase III trials, instead of looking for clues from immune cells, scientists will measure infection rates directly.

Researchers need patients to be challenged with the virus. This way, they can establish the difference between the vaccine and a placebo jab.

Ironically, this is becoming more difficult now. In countries where there are plenty of new confirmed cases, this won’t be a problem.

There’s a “risk” that if the virus disappears today, then the vaccine’s effectiveness cannot be measured tomorrow. If it does, that would be a godsend indeed.



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