Future Vaccine Development May Be Inspired by New Research Findings
Scientists at Boston Children’s Hospital have created an antibody, SP1-77, that successfully neutralizes all tested SARS-CoV-2 variants, including Omicron. Unlike traditional antibodies, SP1-77 prevents the virus from fusing with cell membranes, potentially offering a new approach to virus neutralization and vaccine design.
Therapeutic antibodies that were effective early in the COVID-19 pandemic have lost their efficacy as SARS-CoV-2 has changed and mutated, and more recent variants, particularly Omicron, have learned how to circumvent the antibodies our systems produce in response to vaccinations. We may be able to better guard against possible variations thanks to a new, widely neutralizing antibody created at Boston Children’s Hospital. In tests, it neutralized all known SARS-CoV-2 variants of concern, including all Omicron variants.
“We hope that this humanized antibody will prove to be as effective at neutralizing SARS-CoV-2 in patients as it has proven to be thus far in preclinical evaluations,” says Frederick Alt, Ph.D., of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, who co-led the research.
In a study that was recently published in Science Immunology, Alt and Sai Luo, Ph.D., utilized a modified version of a humanized mouse model that his lab had previously used to look for broadly neutralizing antibodies to HIV, another virus that often mutates. Since the mice effectively have built-in human immune systems, the model closely resembles how the trial-and-error process our immune system uses to create increasingly effective antibodies.
The researchers initially introduced two human gene segments into the mice, causing their B cells to create a wide repertoire of humanized antibodies in a short period of time. They subsequently exposed the mice to the original Wuhan-Hu-1 strain of the virus’s SARS-CoV-2 spike protein, which is the main protein targeted by our antibodies and current vaccines. The modified mice developed nine lineages, or “families,” of humanized antibodies that bonded to the spike in response.
Together with a Duke University team led by Dr. Barton Haynes, Alt and Luo then assessed the efficacy of these antibodies. Antibodies from three of the nine lineages were effective in neutralizing the original Wuhan-Hu-1 virus. The SP1-77 antibody and other members of its lineage, in particular, demonstrated extremely wide activity, neutralizing Alpha, Beta, Gamma, Delta, and all prior and current Omicron strains.
A New Approach to Virus Neutralization
What caused the SP1-77 antibody to be so broadly neutralizing? Structural studies by a collaborating team led by Bing Chen, Ph.D. and Jun Zhang, Ph.D. at Boston Children’s Hospital and the Haynes group at Duke, showed that SP1-77 works differently from current antibodies (either therapeutic antibodies or those we make in response to current vaccines).
Many of the existing antibodies work by attaching to the receptor-binding domain (RBD) of the spike in certain regions, preventing SARS-CoV-2 from binding to our cells’ ACE2 receptors, which is the initial step in infection. The SP1-77 antibody binds to the RBD as well, but in a completely different manner that does not prevent the virus from binding to ACE2 receptors.
Using a novel live-cell imaging platform described in a preprint, collaborators Alex Kreutzberger, Ph.D. and Tomas Kirchhausen, Ph.D., of Boston Children’s Hospital showed that SP1-77 prevents the virus from fusing its outer membrane with the membrane of the target cell. This thwarts the final necessary step that throws the door open to infection.
These features may inform the design of new SARS-CoV-2 vaccines. “SP1-77 binds the spike protein at a site that so far has not been mutated in any SARS-CoV-2 variant, broadly neutralizing current variants by a novel mechanism,” says Kirchhausen.
Reference: “An Antibody from Single Human VH-rearranging Mouse Neutralizes All SARS-CoV-2 Variants Through BA.5 by Inhibiting Membrane Fusion” by Sai Luo, Jun Zhang, Alex J.B. Kreutzberger, Amanda Eaton, Robert J. Edwards, Changbin Jing, Hai-Qiang Dai, Gregory D. Sempowski, Kenneth Cronin, Robert Parks, Adam Yongxin Ye, Katayoun Mansouri, Maggie Barr, Novalia Pishesha, Aimee Chapdelaine Williams, Lucas Vieira Francisco, Anand Saminathan, Hanqin Peng, Himanshu Batra, Lorenza Bellusci, Surender Khurana, S. Munir Alam, David C. Montefiori, Kevin O. Saunders, Ming Tian, Hidde Ploegh, Tom Kirchhausen, Bing Chen, Barton F. Haynes and Frederick W. Alt, 11 August 2022, Science Immunology.
DOI: 10.1126/sciimmunol.add5446
The study was funded by the Howard Hughes Medical Institute, the Bill & Melinda Gates Foundation, the NIH NIAID Consortia for HIV/AIDS Vaccine Development, the Massachusetts Consortium on Pathogen Readiness, Emergent Ventures, the Food and Drug Administration, the NIH Maximizing Investigators’ Research Award, NIH Grant AI163019, the Danish Technical University and SANA, IONIS, and a Harvard Virology Program NIH training grant.
Alt and Ming Tian, Ph.D., at Boston Children’s are authors of a patent application describing the mouse model. Luo, Haynes, and Alt are authors of patent applications describing the antibodies.
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47 Comments
Searching for an antibody that will neutralize all pathogens is like Searching for a key that will open all locks. Antigen/antibody binding is a lock and key phenomenon. An antibody production is provoked by specific Antigenic stimulation. Hence, each antibody will bind and neutralize the specific Antigen that provoke its production. This is fundamental immunological principle. To go in Search of an all conquering vaccine that will provoke the production of an all conquering antibody, is intellectually dishonest.
Your last comment makes no sense.
your entire comment is intellectually dishonest
When has this happened previously Felix Moyo Edonmi?
Felix Moyo Edonmi… thats not true and when you say it is intellectually dishonest, exactly what are your qualifications for yourself being any kind of expert or at minimum even an intellectual about the subject? Just off the top of my head, I can name that shark antibodies don’t operate by binding and neutralization as you state. Shark antibodies will tear thru a cell structure. These are humanized mice antibodies and you are just assuming for some reason that since most purely human antibodies just a binding/neutralization mechanism that all antibodies must. That is a failure of both logic and knowledge on your part.
If we stop the pathogen from fusing its outer membrane with the membrane of our cells thus blocking the lock for all keys what method would a virus use to circumvent that which would be all conquering?
Lest we forget that the protein that has not YET mutated might in the future. So the best outcome is we can through SP1-77 systhesis force the “species ” of virus to extinction. (no hosts no spread no spread extinction. This assumes SP1-77 antibody is given to everyone including the new born ??
A combination of this vaccine and strict infection-control methods could hypothetically eliminate Sars-CoV-2.
One consequence of strict measures to control the spread of Sars-CoV-2 in 2020 was the coincident control of the spread of other airborne viruses. It appears to have eliminated one of the two known lineages of Influenza B. B/Yamagata has not been found in any sample collected since the winter of 2020-21.
In practice, given the politicization and conspiracy theories of vaccination and infection control measures for Sars-CoV-2, there is no hope of us eliminating it.
Is it gOd or gadsend?
“SP1-77 binds the spike protein at a site that so far has not been mutated in any SARS-CoV-2 variant, broadly neutralizing current variants by a novel mechanism,” says Kirchhausen. The virus has not been subjected to these antibodies to any broad degree.
We can only hope that the membrane fusion mechanism depends on the proteins involved in the fusion to be so invariant that any mutation will doom the virus’s infectivity. Otherwise, it may be possible that the selective pressure of exposure to these antibodies may result in new, viable mutations to arise.
This would be a modern development of great importance but for the time being, “ignorance and anti-vaxers” is the biggest problem that we have when it comes to mitigating COVID or any other virus.
A little late enzolytics has the patents, Intel AI, Samsung
This doesn’t explain if this vaccine would prevent further mutations. And if it doesn’t, would there be a risk of a more severe strain of the virus. I’m also confused at how fast COVID has mutated.With HIV, if I recall it took some time to mutate. Also my concern is, how do we know that the current vaccines are not responsible or partly responsible for these rapid mutations? This article is more redundant than informative.
All RNA based viruses mutate quickly, including Sars-CoV-2, Influenza, and HIV. Sars-CoV-2 is not wildly out of line with other RNA viruses.
In the case of HIV, reverse transcriptase is very error prone, and thus prone to introducing new mutations.
Who just announced 54 Billion in profit from Covid vaccine? Bill Gates made billions also. Time to listen to Geert Vanden Bossche, Peter McCullough, Ryan Cole, and 17,000 other doctor’s that signed the Barrington Declaration.
Ivermectin, Hydroxycloraquin, Budesonide WORK. They screwed up Natural Immunity which covid would now be non-existent.
go ahead eat all the ivermectin you can and then tell the world what six feet under looks like
This is a marvelous find by scientists real science not dr fouccie science yes I said it human geniuses they are and should be given the highest scientific prize being the Nobel they earned it
@ Felix Moyo Edonmi
It’s intellectually dishonest to argue against something the article isn’t claiming to have done. It doesn’t say they’ve found an antibody to all pathogens. It says they’ve found an antibody to all known variants of covid. That’s very different.
It does it by targeting a specific antigen, just as you described. It’s just that the antigen in question has not yet mutated, and is therefore the same in all variants.
The obvious caveat is that there’s no guarantee it won’t mutate in the future, particularly under the selective pressure of some, but not all, of the potential viral hosts being vaccinated.
VoterID and ballot verification will take care of this covid-19 problem. It’s all political.
Ummm…no thanks to injecting everybody on the planet with whatever they come up with!!?? To eradicate ?? Nope! For a virus that has only SERIOUSLY affected about 0.3 to maybe 0.5% of population? No thanks.
0.3% to 0.5%, so effectively 1 in roughly 200 or 300. Let me ask you a question about risk management. If one in every 200 airplanes crashed, would you get on one?
Actually the odds of dying in a MVA are like 1 in 100 over a life time so yes. Cars are still worse than thevworst case scenario covid. Also cars take a lot of young lives and don’t target elderly and immune compromised. Stop trying to tell people your grandmother is more important than people’s children. Finally please explain how injecting a healthy person helps the vulnerable when it doesn’t even slow the spread.
If this was the so called solution they would of rolled it out by now but, Americia blowing smoke and mirrors up there ass again. Now the initial vaccines that boost white cells were rolled out with no proof of testing of the product what so ever but now these vaccines are under strict guidelines before even thinking of rolling out there so called cure. Stop wasting time dealing with cells its not even close to the cure of covid 19.
The cure that will come out will be able to alimitate covid 19 through the blood, because the virus never leaves the blood I’m not going to talk about this information to incompant unqualified americians that the government has hidden the real facts up about covid 19 too, not to mention the rest of the world. When the americian government starts telling the truth covid 19 then it will be over and cure solved.
maybe you should learn to spell before having an opinion that is blatantly wrong
What people and scientists forget is that nature has a way of evolving viruses so that any vaccine will in time will be not as effective as seen with the COVID strains. Nature’s number one rule is survival of the fittest. And what doesn’t kill you makes you stronger goes for viruses as well as people.
stop being skeptical, the sp1-77 is going to make covid gone forever!! can’t wait to try it.
– stratos yannikos
umass med. and biological dept. phd.
what i meant was, if trump takes it, then i will. whatever trump does is best for america! Trump rules man!!!
Yay ! Works on the mice they tested for two weeks then euthanized ! Remember kids, this “vaccine” will also not prevent you from getting any of the viruses and was never tested on anything larger than mice ? Kinda strange that ! Also strange is the rapidity of mutation of Covid only fitting explanation is just like the first version is that Fauci still has labs creating and intentionally releasing them. And your local virologist and you’ll find out more than you really want to know ….
Felix Moyo Edonmi you sound like a typical Google Fartfinder.
What a great discovery right here in Boston Children’s Hospital, MA.
Modern science is so incredible. Scientists are simply amazing people how they can figure things out that are completely beyond the reach of regular people.
Over 1 million Americans have died from Covid and hundreds of thousands of them didn’t need to because politics got in the way. How sad
Bill Gates and his foundations have not profited from the development of COVID vaccines.The Billions profited report shown online is a little masterpiece of hacking and creative video/email editing.It has no foundation in fact.
We need a firm commitment to logic and truth to beat COVID.Some mutual respect for each other’s health -and opinions-would be nice,too.
And frogs fly. So sad the false changing narrative evolution of COVID.
Good yes
If it’s real and not a lie the next question is how to get people to get vaccinated with it because sooner or later before the end of this year there will be a variant of covid-19 in America that the vaccines provide no protection what so ever thanks to the Republicans who want to decrease the population of America to gain power that’s why they went with the fiction of spontaneous heard immunity Wich has never existed and it involves 80% of the population to die for a fictional 20% to live.Why else was the first order one that spread the covid-19 pandemic throuout all of America in one month it the beginning of the pandemic??? Everyone crowd together and get covid-19 virus have kids go to school and come home as carriers of covid-19 call people on planes and that will spread covid-19 even faster throughout America sound familiar???This is the blunt truth of all republicans everything for them and a big crowd of starving people to be envious of those who have food. under no circumstances do they help anyone but themselves and they think they should get away with what ever they want.
OMGOSH….Talk about conspiracy theories I am afraid you are deep in up to your eye balls if you think the democratic party is any better. In my opinion all of the so called politicians in DC are nothing more than crooks. There needs to be a huge clean house and start with fresh decent people who truly care about our country and WE THE PEOPLE in it. Otherwise COVID is nothing of what is to come.
It’s not about eradicating the virus. The host needs to be less inviting, less accessible, more combative
Absolutely right. Your statement is the Most accurate thing said here. Thank you
It is important to search for the right thing hung up by the variants in general.
Actually I have a master key to our office that opens all doors, desks, and cabinets. I don’t really get the reference since master keys do exist.
For me personally, this is the most oromising thing I have read in a while. Yes to targeting a part of the virus that is not mutating as quickly. Makes sense. But to still mask and ventilate and try to slow transmission at the same time.
I just read all of the comments here. Some of you sound fairly educated, some need to learn how to spell, and some are just plain stupid! I applaud the research, the science and scientists that are giving giving their time and in some cases, their lives to combat this horrible viral infection, while at the same time battling anti-vaxers and conspiracy theorist’s every step of the way! I say, “if you know what you’re talking about and can contribute for the good, share it!
If you don’t, and pretend like you do… Stop the act, and shut your f-ing mouths! We have enough problems already, we don’t need your ridiculous sociopathic nonsense! I mean, Where is all of your research, hmmm? Not hear say, RESEARCH? …. POST IT!
Professor Brainiac and his team of half wits! SMFH
No thanks, keep your poison shot. My body’s immune system will do what it does best, besides Covid is nothing more then the common cold.
Yes Tom, because the common cold hospitalizes and kills people, pushing our medical system to the limit. I had a mild case, others are not so lucky.
Let’s just clear something up. Vaccination rates have been exceedingly high many countries yet it didn’t make a lick of difference. The virus mutation had the biggest effect on numbers. Get off this anti vaxer nonsense. Hold these pharmaceutical companies accountable for getting us to pay for these multi trillion dollar snake oil vaccines that are far less effective than any vaccine approval by FDA in history. Most Vaccines work well but Pfizer and Moderna mRNA covid vaccines seem to only suppress people’s immune systems.
Covid Vaccinations/Flu shots (which I’m grouping together based on current data) have some evidence of benefiting elderly and immune compromised but have repeatedly(long term data from flu shots) showed basically 0 benefits to healthy individuals and 0 effects on reducing transmission. It’s like taking a vitamin for a nutrient that is abundant in your diet. It has the potential to actually do harm and no possibility to improve your outcome.
This is all about money, no one cares about people ! I’m still unvaccinated, meanwhile my vaccinated friends have had up to 3 reinfections.