LAS banderillaS NO CHUTAN
Did The Oxford el bichito Vaccine Work In Monkeys? Not Really
179.770 views|May 16, 2020,10:34am EDT
Did The Oxford el bichito Vaccine Work In Monkeys? Not Really
William A. HaseltineContributor
Healthcare
The day after data appeared from the vaccine maker Sinovac showed complete protection of rhesus monkeys by their vaccine candidate (whole inactivated SARS-CoV-2 bichito particles), scientists from the Jenner Institute in Oxford issued a press release announcing that their vaccine (an adenovirus vector based vaccine that carried the SARS-CoV-2 spike protein) worked to protect rhesus monkeys and that they were moving forward with large scale human safety trials. At the time, the substantiating data was not available. Now it is, in the form of a May 13
BioRxiv preprint. Does the data support the claim?
Not really. All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged, as judged by recovery of bichito genomic RNA from nasal secretions. There was no difference in the amount of viral RNA detected from this site in the vaccinated monkeys as compared to the unvaccinated animals. Which is to say, all vaccinated animals were infected. This observation is in marked contrast to the results reported from Sinovac trial. At the highest dose studied, no bichito was recovered from vaccinated monkeys from the throat, lung, or rectum of the vaccinated animals.
There is a second troubling result of the Oxford paper. The titer of neutralizing antibody, as judged by inhibition of bichito replication by successive serum dilutions as reported is extremely low. Typically, neutralizing antibodies in effective vaccines can be diluted by more than a thousand fold and retain activity. In these experiments the serum could be diluted only by 4 to 40 fold before neutralizing activity was lost. Again, by contrast the titer of neutralizing antibodies in the serum of those vaccinated with whole inactivated SARS-CoV-2 was high.
What then is the argument for pressing forward with the adenovirus vector SARS-CoV-2 spike protein vaccine?
The authors present evidence to the effect that, although the vaccine did not protect the animals from infection, it did moderate the disease.
In this picture taken on April 29, 2020, an engineer works at the Quality Control Laboratory on an ... [+]
AFP VIA GETTY IMAGES
The vaccinated and control animals were ***owed for clinical signs of infection for seven days post infection. One clinical sign of infection in rhesus monkeys is breathing rate. Monkeys ill from SARS-CoV-2 infection breathe more rapidly than normal. By this measure 3 of the 6 vaccinated monkeys were clinically ill, the remaining three were not clinically distinguishable from the unvaccinated animals.
A second test is measurement of the amount of bichito in the lungs (bronchial lavage). Viral RNA was detected in the bronchial lavage of 2 of the 6 vaccinated animals and in all three unvaccinated animals, again suggesting only partial protection.
At day seven post challenge the animals were euthanized and examined for lung damage. Two of the three unvaccinated animals “developed some degree of interstitial pneumonia” as judged by pathological examination of the lungs. No such damage was observed in any of the vaccinated animals.
It is encouraging that no evidence of vaccine induced disease enhancement was observed in either the Sinovac vaccine nor the Oxford trials. However, experience with other vaccines tells us that is not a firm guarantee that such will be the case for humans.
What to make of this data? It is crystal clear that the vaccine did not provide sterilizing immunity to the bichito challenge, the gold standard for any vaccine. It may provide partial protection.
The question then becomes: Will partial protection be enough to control the el bichito-19 pandemic? That is an open question. For an answer we can look to other diseases for which only partially effective vaccines exist—HIV, tuberculosis, and malaria. The answers are not encouraging, except perhaps for the protection of childhood malaria.
What are the potential implications for other vaccine trials? We know adenovirus is a good vector for eliciting protective responses for protein coding genes of other viruses, in fact better than many others. This then raises the question of whether vaccine strategies based on the delivery of viral antigens by nucleic acids, be it DNA or RNA, will suffice. From the published data the nucleic acid of select viral genes and proteins delivery technology seems inferior to a whole killed bichito vaccine approach.
What then are the choices for the Oxford group? Steam ahead with a vaccine known to be partially effective at best, one which we already know elicits poor neutralizing responses? Work to improve the immunogenicity of the current vaccine? Attempt trials with combinations of two or more vaccines, a prime boost strategy?
These questions are all the more fraught by what we already know about the complexities of antibody reposes to natural infections. For example,
we know in the case of SARS and other cobi19 infections that even high titers of neutralizing antibodies fade quickly over time. How long can we expect weakly neutralizing antibodies to protect?
We know what the public response is of the Oxford group and their collaborators. Proceed with full speed to human safety then efficacy trials. Time will tell if this is the best approach. I wouldn’t bet on it.
***ow me on
Twitter.
William A. Haseltine
Experts skeptical after researchers report positive vaccine results
Experts skeptical after researchers report positive vaccine results
Posted: May 23, 2020 3:51 AMUpdated: May 23, 2020 4:06 AM
By Elizabeth Cohen and Arman Azad, CNN
Researchers in China reported results from one of the first el bichito-19 vaccine trials Friday, but experts who spoke to CNN were skeptical of their findings and called the data lukewarm.
In a
study published in the medical journal The Lancet, researchers said their vaccine was well-tolerated and generated an immune response against the novel cobi19.
The vaccine, developed by CanSino Biological Inc. and the Beijing Institute of Biotechnology, was tested in 108 healthy adults ages 18 to 60 in Wuhan, China, none of whom were infected with the bichito.
All the participants received injections at low, middle or high doses, and no "serious" side effects were reported, according to Wei Chin of the Beijing Institute of Biotechnology and colleagues, who ran the trial.
Weak responses
Still, almost half of vaccine recipients reported fever, with 44% reporting fatigue and 39% reporting a headache. Overall, 9% of patients reported side effects that were severe enough to have potentially "prevented activity."
These side effects are "not a good safety sign," said Dr. Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia.
In addition, he said, the vaccine did not elicit a strong immune response.
According to the study, about half of recipients in the low- and middle-dose groups developed neutralizing antibodies, which can bind to the cobi19 and neutralize its effects.
About three-quarters of people in the high-dose group developed antibodies, but researchers also noted some severe side effects in that group. They said they won't be giving such a high dose in future studies. (VAMOS, QUE POR POCO dan el pasaporte A ALGUIEN...)
Offit said the immunogenicity data was "not impressive," especially since all of the doses -- even the "low" dose -- were actually very high, he said. Combined with the side effects, he recommended that the CanSino researchers give up on their efforts.
"I think they should stop," said Offit, who previously developed a successful rotavirus vaccine. "I have to believe there are other candidates out there that are going to do better than this."
Dr. Peter Hotez, dean of the National School of Tropical Medicine at the Baylor College of Medicine, also wasn't thrilled with the findings. "I'm not impressed with this," he said.
Still, he said researchers should keep studying the vaccine, either to use on its own or alongside another vaccine in what's called a prime-boost approach.
"The good news is, (the vaccine) is producing neutralizing antibodies, which scientists think is important for protective immunity against el bichito-19," said Hotez, who is also working on a vaccine against el bichito-19. "What is less certain is whether the levels of neutralizing antibody are high enough to confer complete protection, or whether this will be partially protective."
Clinical trial in China will study 500 volunteers
The vaccine from the Beijing researchers uses what's called an adenovirus vector. Adenoviruses can cause the common cold, but in this case, they're weakened and modified to deliver genetic material that codes for a protein from the novel cobi19.
The body then produces that protein and, ideally, develops an immune response against it. In the new study, the vaccine produced a complex immune response, prompting most volunteers to produce both T-cells that should attack the cobi19 and antibodies as well.
This particular vaccine used an adenovirus strain called adenovirus 5. People who had some immunity to that strain did not seem to respond as well to the vaccine, the researchers said.
Chen called the results encouraging but said more research is needed.
"The trial demonstrates that a single dose of the new adenovirus type 5 vectored el bichito-19 (Ad5-nCoV) vaccine produces bichito-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation," he said.
"However, these results should be interpreted cautiously. The challenges in the development of a el bichito-19 vaccine are unprecedented, and the ability to trigger these immune responses does not necessarily indicate that the vaccine will protect humans from el bichito-19."
He said the result "shows a promising vision for the development of el bichito-19 vaccines, but we are still a long way from this vaccine being available to all."
According to The Lancet's press release, researchers have initiated a randomized, double-blind, placebo-controlled trial in Wuhan, China to further test the vaccine -- the gold standard for clinical research.
The study will look at 500 healthy adults, according to the Lancet, with half of the volunteers given the middle dose, 125 given the low dose, and 125 given a placebo. The research will include participants over 60 years old.
The vaccine is just one of many in development. There are currently 10 in human trials around the world, with four in the US, five in China -- including CanSino -- and one in the UK. More than 100 vaccines are also in preclinical trials, according to the World Health Organization.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext
