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COVID-19: New Results Shine Ray of Hope on Vaccine Development Efforts

COVID-19: New Results Shine Ray of Hope on Vaccine Development Efforts

Photo: Artem Podrez/Pexels.

On March 11, 2020, amidst mounting pressure from the global scientific community, the WHO declared the coronavirus outbreak to be a pandemic. Ever since, the spread of the novel coronavirus has assumed epic proportions, with more than 14.5 million confirmed cases and 607,781 deaths by July 23.

The outbreak has strained already overburdened public healthcare systems worldwide, and exposed glaring lacunae in current pandemic preparedness frameworks. Even so, and in spite of global epidemiological surveillance, the emergence of COVID-19 is not a complete surprise.

A significant proportion of COVID-19 mitigation and containment efforts have focused on the development of vaccines against the virus, SARS-CoV-2. Amidst a surge in infections worldwide, the development of a safe, effective and affordable coronavirus vaccine in the near future is the best hope for eventually ending the pandemic. There are currently 24 candidate vaccines in clinical trials and 142 in preclinical development. This is a staggering number for a disease that emerged in only late 2019.

New results from early phase clinical trials of promising candidate vaccines are a glimmer of hope. One of the frontrunners in global vaccine efforts is the experimental vaccine developed by Oxford University, in partnership with AstraZeneca, called ChAdOx1 nCoV-19 (or AZD1222). Findings from a Phase 1/2 clinical trial of this candidate vaccine published on July 20 are promising. The ChAdOx1 nCoV-19 vaccine elicited robust immune response against the virus in study participants, with minor side effects.

Most vaccines work by activating either one or both arms of the immune system. Effective vaccines elicit protective antibodies that prevent further infection, and/or activate long-lasting immunological ‘memory’ mediated by immune cells, called T-cells. The ability to memorise encounters with a previously unknown microbe is a defining feature of the immune system. Vaccine development efforts harness this feature and train the immune system to effectively fight against future encounters by the same pathogen.

Coronavirus vaccines however are unlikely to confer lifelong immunity, and an effective vaccine is expected to be protective for at least six months at a time.

But even with accelerated research into COVID-19 vaccine development, not much is known about the immune correlates of protection against SARS-CoV-2. These refer to measurable biological markers that define a vaccine-induced immune response against the virus, such as levels of protective antibodies or T-cells. Immune correlates can tell us how effective a vaccine is and predict how protective it can be in populations other than the one in which it was tested. These correlates also guide the design and testing of improved vaccines.

The Oxford-AstraZeneca ChAdOx1 nCoV-19 is a viral-vectored vaccine, which uses a non-infectious chimpanzee virus (‘vector’) as a vehicle to deliver the gene for the SARS-CoV-2 spike protein into human cells. The phase 1/2 clinical trial was carried out in 1,077 healthy human adults, aged 18-55 years. Ethnic representation was heavily skewed, with 91% of the recruited participants being white. Phase 1/2 clinical trials evaluate safety, dosage and side effects of a potential vaccine, with phase 2 participants receiving the highest dose that did not cause adverse effects in phase 1.

Approximately half of these individuals received the ChAdOx1 nCoV-19 while the other half received an unrelated vaccine as a comparison. In addition, ten of the study participants received two doses of the ChAdOx1 nCoV-19 vaccine in a prime-boost immunisation regimen, with the second dose being administered 28 days after the first.

The vaccine produced protective antibody and T-cell responses against SARS-CoV-2. The levels of antibodies peaked 28 days after vaccination and levels of T-cells peaked after 14 days. Although there were no serious adverse reactions to the vaccine, mild to moderate side-effects were observed. About 70% of the participants developed fever or headache, which required treatment with paracetamol.

In addition, this study does not shed light on vaccine efficacy in older adults, a key target of COVID-19 vaccination, since the upper age limit of participants was 55 years.

Antibody responses were evaluated in a fraction of study participants. Researchers observed the elicitation of protective antibodies in 91% of the study subjects who received one dose (32 out of 35) and 100% (nine out of nine) of the subjects who received two doses of the vaccine. These results indicate that antibody responses can be increased with the second dose, but further validation is required from larger phase 3 clinical trials. This phase 1/2 clinical trial is still ongoing and it is too soon to predict the longevity of these immune responses – i.e., if the vaccine induced immunological memory.

The phase 3 clinical trial of the Oxford-AstraZeneca vaccine was kicked off with thousands of participants, mostly from the UK but also from the US, Brazil, South Africa and India. It remains to be seen if the phase 3/4 trials of this vaccine will reproduce or improve vaccine efficacy observed in the phase 1/2 trials.

AstraZeneca plans to produce and distribute two billion doses of their vaccine by early 2021. To this end, it has signed a licensing deal with the Serum Institute of India to produce one billion doses for low- and middle-income countries. In a statement, Serum’s CEO Adar Poonawalla pledged to commit half of the doses for India, which he hopes will be distributed for free through government immunisation programmes.

Although the results from this clinical trial seem quite promising, there are a number of other, equally promising vaccine candidates. The second (and only other) coronavirus vaccine in phase 3 clinical trials right now is another viral-vectored vaccine produced by China-based CanSino Biologics. In results from a phase 2 clinical trial of this candidate vaccine, published on July 20, the vaccine was found to be safe and induced immune responses with a single dose.

Although this study involved fewer participants than the Oxford study, it included older adults, aged 55 years and above. Not surprisingly, vaccine-induced antibody responses were found to be lower in older adults, who are at higher risk for developing COVID-19.

Other players also in close competition include the US-based Moderna Therapeutics, which will begin the trial of their mRNA-1273 vaccine in 30,000 healthy participants from July 27. Preliminary data from the US-German collaboration between Pfizer and BioNTech also showed promising results, albeit in a smaller number of study participants.

With herculean efforts underway in the race to develop a coronavirus vaccine, small victories do make us optimistic, but it is important to remember that it is too early to jump to conclusions about vaccine efficacy. The real test of the experimental vaccines will be in the phase 3 clinical trials. Let’s keep our fingers crossed!

Rohini Datta is a postdoctoral researcher in genetics at the Stanford School of Medicine, Stanford University. She holds a PhD in molecular biophysics from the Indian Institute of Science, where she worked on HIV vaccine design. All views expressed are her own. She tweets at @dattarohini.

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