And now ...
But this time, they may well be on their way - accompanied by a Chinese team from Wuhan ... and some encouraging results from vaccine trials:
Oxford coronavirus vaccine triggers immune response, trial shows
Early results also indicate vaccine is safe, raising hopes it could help end pandemic
Oxford University’s experimental coronavirus vaccine is safe and generated a strong immune response in about 1,000 people who volunteered to help trial it, researchers have said, raising hopes it could help end the pandemic.
The results published in the Lancet medical journal are preliminary, with the effect of the vaccine measured by the amount of antibodies and T-cells it generates in the blood of the volunteers – not in any response to the virus itself.
Large-scale trials have begun in Brazil and South Africa, however, where infection rates are still high and it will be possible to assess whether vaccinated individuals are less likely to get Covid-19 than others.
The results were “a really important milestone” on the path to a vaccine, said the study’s lead author, Professor Andrew Pollard. They showed that the vaccine was very well tolerated by more than 1,000 volunteers. “We are seeing exactly the sort of immune responses we were hoping for, including neutralising antibodies and T cell responses, which, at least from what we’ve seen in the animal studies seem to be those that are associated with protection.”
The problem is, he said, “we just don’t know what level is needed if you meet this virus in the wild, to provide protection, so we need to do the clinical trials and to work that out.”
Hopefully they would find out from the trials to come what level of immune response is needed, which would help all vaccine developers.
“We don’t know what high is. We’ve got immune responses that we can measure we can see the virus being neutralised when the antibodies are tested in the laboratory, but we don’t know how much is needed. I mean it’s encouraging but it’s only the first milestone on this this long path,” he said.
Ideally the vaccine would protect against any infection, but scientists already accept it may reduce the severity of the disease instead, meaning people would be less likely to become very sick and die.
The volunteers have been followed up for eight weeks so far after immunisation.A further question is how long any immune response will last – if for only six months or a year, people might need regular booster shots.
There are also big questions over whether it will work in older adults – flu vaccinations do not give as much protection to older people, whose immune systems function less well than younger people’s. The trial participants were between 18 and 55 years old. The risk of dying from Covid-19 rises dramatically with age from about 65. Trials are now being undertaken in an older age group.
“The immune system has two ways of finding and attacking pathogens – antibody and T-cell responses. This vaccine is intended to induce both, so it can attack the virus when it’s circulating in the body, as well as attacking infected cells,” said Pollard.
“We hope this means the immune system will remember the virus, so that our vaccine will protect people for an extended period. However, we need more research before we can confirm the vaccine effectively protects against Sars-CoV-2 infection, and for how long any protection lasts.”
If you want the real peer-reviewed deal, you can download a pdf of the article in
The Lancet here:
https://www.thelancet.com/lancet/articl ... 20)31604-4
Of course this just a set of encouraging results, and there is no guarantee that a vaccine effective en masse will result. Still, it's better than a slap in the face with a wet fish, isn't it?
(Wouldn't it be nice, though, if a team of scientists from Wuhan helped produce a vaccine that really worked? How annoyed Trump would be ... unworthy thought!)
The Lancet also has a more accessible comment on the significance of this and the Wuhan trial:
https://marlin-prod.literatumonline.com ... 316111.pdf
Dystopian realities generate utopian visions. The dramatic emergence of SARS-CoV-2 into our lives and the subsequent COVID-19 pandemic have spawned the active development of nearly 200 vaccine candidates.1 Science reveals itself to the world in real time in all its glorious uncertainties, but also in all its careful, hard- won, and real achievements. As COVID-19 vaccine trials progress rapidly and with much expectation, two such achievements are published in The Lancet.2,3
The results of two early phase COVID-19 vaccine trials2,3 are reported, one from investigators at the Jenner Institute at Oxford University (Oxford, UK), with support from AstraZeneca, and the second from investigators supported by CanSino Biologics in Wuhan, China. Both groups used an adenoviral vector, and both report the vaccine achieving humoral responses to the SARS-CoV-2 spike glycoprotein receptor binding domain by day 28 as well as T-cell responses. Both report local and systemic mild adverse events such as fever, fatigue, and injection site pain. In neither trial was a severe adverse event reported.
Andrew Pollard and colleagues report2 their phase 1/2 randomised trial of one injection of chim- panzee adenovirus-vectored COVID-19 vaccine. Vaccine formulation at one concentration was tested against a comparator quadrivalent conjugate meningococcal vaccine among 1077 healthy adults (50% male, 90·9% white) aged 18–55 years (median 35 years, IQR 28–44), recruited from five centres in the UK and followed up for 28 days. Local and systemic adverse events such as fatigue, headache, and local tenderness occurred commonly in COVID-19 vaccinees, but were tolerable and mostly ameliorated by paracetamol. No serious adverse events occurred. Neutralising antibodies were generated in more than 90% of participants across different assays. Responses were sustained up to 56 days of observation. A small non-randomly selected, second-dose boosted subset showed strong neutralising responses, and few mild adverse events. Importantly, T-cell responses were induced in all participants.
Wei Chen and colleagues report3 results from a phase 2 randomised trial of one injection of non- replicating adenovirus-vectored COVID-19 vaccine. Vaccine formulation at two concentrations (ie, 1×1011 or 5×1010 viral particles per mL) were tested against placebo among 508 healthy COVID-19 unexposed adults
(50%male)aged18-83years(mean39·7years)recruited from one centre in Wuhan, China, and followed up for 28 days. Adverse events such as fever, fatigue, headache, or local site pain occurred by day 28 in 294 (77%) of 382 vaccinees and 61 (48%) of 126 placebo recipients. Male sex was associated with lower occurrence of fever post-vaccination. No serious adverse events occurred. Seroconversion occurred in more than 96% of participants, and neutralising antibodies were generated in about 85%. More than 90% had T-cell responses. People older than 55 years of age had somewhat lower humoral responses (although still higher than placebo), as did people with previous vector immunity, but these factors did not affect T-cell responses. Immunogenicity did not differ by sex.
These trial reports are hugely anticipated. The results of both studies augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety. Overall, the results of both trials are broadly similar and promising, notwithstanding differences in the vector, in the geographical locations of the populations studied, and the neutralisation assays used. Without drawing causal inference, the exploration of associations of age and sex with adverse events and immunogenicity reported by Chen and colleagues, and of longevity of response by Pollard and colleagues, are welcomed, given the differential burden of severe outcomes in older adults, and the emerging science around differential sex-specific vaccine effects.4 These COVID-19 vaccine trials are small so inferential caution is warranted, but theexplorationsarelaudable.Ethnicdiversityinboth these trials was very limited.
Both trials used adenovirus vectors to deliver and study the COVID-19 vaccine, an innovative and efficient means of vaccine development in the midst of a pandemic. Capable of generating humoral, cellular, and innate responses, adenovirus-vectored vaccines have much potential. The platform only achieved European Commission regulatory licensure on July 1, 2020, with the Ebola vaccine. Much remains unknown about these and other COVID-19 vaccines in development, including longevity of response and immunogenicity in older adults or other specific groups, such as those with comorbidities who are often excluded from clinical trials, or ethnic or racial groups more severely affected by COVID-19.5–8 What should phase 3 trials look like? They should be rapid, pragmatic, and large enough to address efficacy in subgroups of interest. Will a single dose be sufficient in older adults, or is a booster dose required? Does longevity of response or rates of waning differ with a two-dose regimen, and does longevity of clinical protection require cell-mediated responses? Are there host-specific differences in immunogenicity by age, sex, or ethnicity? Do T-cell responses correlate with protection irrespective of humoral titres? Are there specific adverse events in pregnant women? As hotspots for infection shift, trial designs that are responsive to differential risk, or that are enriched for networks of infection, should be deployed.
The safety signals from these two important trials are reassuring. But when things are urgent, we must proceed cautiously. The success of COVID-19 vaccines hinges on community trust in vaccine sciences, which requires comprehensive and transparent evaluation of risk and honest communication of potential harms. Hand in hand with the trajectory of vaccine study, pharmacovigilance infrastructure is urgently needed, including surveillance for asymptomatic infection among vaccinated and unvaccinated persons if both
absolute and relative risk of adverse vaccine outcomes, such as enhanced disease, are to be determined.9 These should be implemented in parallel with phase 3 trials and in preparation for phase 4 roll-out. Such infrastructure will be needed across a wide range of populations and settings, and for the spectrum of upcoming COVID-19 vaccines.
Equitable distribution of future COVID-19 vaccines also requires detailed evaluation of local country needs and priorities, community engagement, and trust. Global planning is underway,10,11 but should be underpinned and informed by specific local realities. Only this way can these very encouraging first early- phase randomised trial results yield the global remedy for which we all yearn.
