TL;DR: Our well-diversified “stock portfolio” of vaccine candidates is demonstrating strong first-quarter returns. Still too early to predict annual fund performance.
More information:
A partnership between Oxford and AstraZeneca released data last week indicating that their vaccine candidate is SAFE and SPARKED AN IMMUNE RESPONSE in trial participants. Another team from the Chinese biotech CanSino concurrently published early data about their vaccine candidate in the same scientific journal (links below). They also found hopeful signals about SAFETY and IMMUNE RESPONSE. Both team’s studies were well-designed randomized controlled trials published in a top-flight scientific journal.
The Oxford-AstraZeneca and CanSino candidates now join the ranks of others with promising early data, including the highly visible Moderna vaccine candidate [see earlier Dear Pandemic post here: https://bit.ly/3jtI2E7] and Pfizer-BioNTech candidate in the news cycle today (link below). Yay!
But….and y’all have learned that we scientists always have a “but!” interjected into the conversation…..the data are best understood as promising signals and even the lead investigators of the above studies admit to NPR that “there’s still plenty that can go wrong” (link below).
So what’s next? Larger randomized controlled trials – with study populations in the tens of thousands – that are “pivotal” for FDA approval.
OPEN QUESTIONS GOING INTO THESE STUDIES:
(1) ARE ANY OF THE PROMISING CANDIDATES ACTUALLY EFFECTIVE?
Evidence-to-date can only speak to a lack of serious, commonly occurring adverse side effects and proof-of-concept about biological mechanisms of action. The jump from hypothesized biological mechanism(s) to actual disease prevention is a major one – and sadly, a fraught one, as historically many vaccine candidates have failed to clear this hurdle.
(2) WHAT’S THE RIGHT DOSE?
Optimal dosing is a tricky dance. There’s often a tradeoff between OOMPH and SAFETY – higher doses can pack a bigger protective punch, but often also lead to more and more serious side effects.
(3) ARE THERE RARE SIDE EFFECTS?
While initial, smaller-scale studies such as the ones discussed above* can provide important information about common side-effects, they lack sufficient sample sizes to credibly detect those that are rarely occurring. The larger sample sizes of the pivotal trials now launching will provide a better portrait regarding the potential emergence of rare side effects. Note that continued monitoring of even larger-sized populations will take place after FDA approval, providing additional safety data.
(4) WILL THE VACCINE(S) WORK IN OLDER INDIVIDUALS?
As described in a wonderful Wall Street Journal article (link below), our immune systems lose strength over time as we age. As a result, it can be more difficult to develop and deploy effective vaccines for older individuals. This concern holds for the current setting – for example, the CanSino vaccine target did not perform well in older people (see StatNews article below) – and is particularly troubling given that older individuals are at higher risk of poor outcomes resulting from Sars-CoV-2 infection. The next generation of vaccine research will explore potential solutions – including, for example, the possibility of giving immune system boosters (aka “adjuvants”) to older individuals.
Other interesting points of note:
The FDA recently announced a “how good is good enough?” threshold: The FDA has determined that a vaccine must demonstrate a 50% improvement in protection relative to placebo to be granted approval. Note that this threshold is in the range of protective effects conferred by flu vaccine – which has fluctuated between 19% – 60% in recent years – but lower than the WHO ideal of 70%. (See links below for more information)
More context on the immune responses witnessed in the two studies above: Professor Adrian Hill, an investigator on the Oxford-Astra Zeneca team, describes a “two-pronged” immune reaction as the ideal, leading to both an increase in antibodies as well as a T-Cell response. As NPR helpfully describes, “the antibodies prevent healthy cells from becoming infected, and the T-cells work to kill cells that have already become infected.” (link below). Be on the lookout for an upcoming Dear Pandemic post on this topic!
In summary, this Nerdy Girl (Lindsey) remains hopeful about emerging vaccine data. And we promise to keep you up-to-speed as new data emerge on the scene!
[Full disclosure: Other scientists who I hold in great esteem remain less sanguine. Alas, only time will tell.]
REFERENCES:
Lancet publication, Oxford-AstraZenca
Lancet publication, CanSino
Pfizer candidate – manufacturing deal brokered with U.S. government
Wall Street journal article on vaccination and older populations
NPR article on Oxford-Astra Zeneca results
FDA guidance document re: 50% threshold
Related reporting: Link 1 and Link 2
Great overview of vaccine candidates and their various biological mechanisms of action
StatNews’ terrific (!) tracker of latest vaccine developments
*CanSino sample size ~500 participants; Oxford-AstraZeneca sample size ~1,000
