New HIV vaccine with a 97% antibody response rate in phase I human trials

https://www.europeanpharmaceuticalreview.com/news/141892/novel-hiv-vaccine-approach-shows-promise-in-landmark-first-in-human-trial/

by MKais • 5 years ago

664 193 5 years ago

europeanpharmaceuticalreview.com

nickthemagicman3• 5 years ago

I don't understand this well enough to fully know how this vaccine works.

But HIV integrates into the human genome so you can never really get rid of it. So I'm not sure exactly how this treatment would play out.

zizee• 5 years ago

Vaccines trigger an immune response, preparing the body to fight of the infection. This allows the body to "beat" the infection before it takes hold.

Afaik vaccines are not useful after the fact. I.e. this HIV vaccine won't be given to people already infected.

nickthemagicman3• 5 years ago

Right but for a virus that integrates into the genome once it takes hold it's game over.

And even vaccine mediated immune responses are via memory cells and take time to ramp up to generate the antibodies to attack the virus.

So I guess my question is: Is the window of opportunity while ramping up the immune system for a vaccine big enough for HIV to take root in a body.

Does your knowledge stop at "Vaccine stop infection?" Isnt that just common knowledge?

frostburg• 5 years ago

There are various exceptions. HPV vaccines for example are useful after the fact.

sp3322• 5 years ago

You can keep it from spreading quickly within a person's body, and reduce the chances of transmission, if you can reduce the amount of viral particles that exist outside of host cells.

nickthemagicman3• 5 years ago

Seems like even vaccine mediated immune response takes time to ramp up and generate antibodies.

Especially from memory cells.

I don't know if that window of opportunity is sufficient for HIV to integrate into the host genome.

thescribbblr• 5 years ago

I am confuse about the working of this vaccine? Anyone, who can make me understand about the working I would be thankful.

arrosenberg2• 5 years ago

They developed a piece of mRNA that produces a specific type of blood protein that binds the HIV infection mechanism. The bound protein triggers your body’s antibody cascade to attack and neutralize it.

agumonkey• 5 years ago

is that similar to what is being investigated for cancer ?

ignoramous• 5 years ago

From TFA to set context: The vaccine is an immune primer, to trigger the activation of naive B cells via a process called germline-targeting, as the first stage in a multi-step vaccine regimen to elicit the production of many different types of broadly neutralizing antibodies (bnAbs). Stimulating the production of bnAbs has been pursued as a holy grail in HIV for decades.

That is, the vaccine triggers generation of bnAbs successfully, turning a "passive immunization" HIV/AIDS treatment in to "active immunization".

More on bnAbs:

Antibodies are proteins that immune cells make to block viruses and other infectious agents. In the case of HIV, people who are infected typically produce antibodies to the virus. But because the virus mutates and replicates rapidly, antibodies are largely ineffective at controlling the virus. After years of infection, though, some people produce highly potent antibodies called broadly neutralizing antibodies (bnAbs) that, in laboratory tests, are able to neutralize a wide variety of HIV strains. The identification of such antibodies has transformed the field of HIV prevention research for two reasons: it provides information to guide the design of vaccines that could elicit bnAbs for protection, and it has opened the door to a new prevention modality: the administration of HIV bnAbs to prevent infection.
The administration of antibodies to prevent infection is known as passive immunization, in contrast to active immunization, which occurs as a result of vaccination (see graphic, below). While a vaccine “trains” the immune system to generate antibodies and other immune responses, passive immunization requires that the antibodies be delivered directly into the body through infusions or injections. This protection is temporary, and, in the case of HIV prevention, would need to be administered periodically as long as the subject was still at risk.

From: https://www.iavi.org/our-science/bnabs-for-hiv-prevention

xiphias2• 5 years ago

This looks to be the original announcement from February: https://www.iavi.org/news-resources/press-releases/2021/firs...

Browsers not showing full URLs were the first bad thing, but now articles are linking to domain names, which makes those links unusable for cross-checking references.

dj_mc_merlin• 5 years ago

Interested to hear from people in the know: how good does this look?

dheera• 5 years ago

Interested to hear the same.

In particular, how easy will distribution be, considering that HIV is extremely easily preventable but it still spreads, because of lack of distribution of knowledge, I assume.

taurath3• 5 years ago

Cost is the largest factor. HIV could be nearly eliminated entirely if PREP wasn’t a cash cow for Gilead.

heavyset_go6• 5 years ago

In particular, how easy will distribution be, considering that HIV is extremely easily preventable but it still spreads, because of lack of distribution of knowledge, I assume.

This is a huge problem in the US. Truvada must be taken everyday to prevent HIV, and in 2015, it cost $1400 for a 30 day supply. In 2021, it costs between $1900 and $2500+ for a 30 day supply in the US.

Elsewhere in the world, Truvada might cost $40. In Australia, Truvada costs $8 for a 30 day supply[1].

The only other drug approved for PrEP in the US is Descovy, which is manufactured by Gilead, too, and costs $2300+ minimum for a 30 day supply.

[1] https://www.independent.co.uk/news/world/americas/us-politic...

peter3032• 5 years ago

15,000 people a year still die in the US with HIV.

https://www.hiv.gov/hiv-basics/overview/data-and-trends/stat...

ufo• 5 years ago

This vaccine doesn't prevent infection by HIV so it's not ready for real world use. What it does is prime the immune system so that a second vaccine might become more effective. The second vaccine still needs to be developed though

Blikkentrekker2• 5 years ago

H.i.v. spread is not so easy to prævent as many think.

Many seem to think that the use of a condom turns transmission risk from 99% to 0% or something along those lines.

The reality is more so that it changes 1% to 0.3%, and it heavily depends on the sex act and direction of transmission as well.

Another not so often sung fact is that the transmission rate from patients who take blockers properly, and thus have an undetectable viral load is 0%.

https://www.aidsmap.com/about-hiv/estimated-hiv-risk-exposur...

eli2• 5 years ago

Distribution? There’s no evidence that it works yet

briefcomment• 5 years ago

Does this require everyone to get it?

colinmhayes2• 5 years ago

HIV is sexually transmitted, so only sexually active people would be required to get a vaccine.

nkozyra• 5 years ago

The high risk group is larger than that, though.

mekster• 5 years ago

Wtf are you talking about?

SquareWheel2• 5 years ago

Drug users are also high risk, as are any medical professionals that work around needles.

yarg2• 5 years ago

You left out transmission via blood.

mike006323• 5 years ago

The public health community learned a hard lesson from this mentality with the HPV vaccine. Many young girls did not get the vaccine because they (or their parents) insisted they were not and would not be sexually active. The CDC recommendations for who should get the vaccine (which controls whether insurance covers it and whether military members are eligible to receive it) expanded from young girls to all people under 27, then to all people under 45.

Regarding HIV, why not get vaccinated if you have easy access to it? What is the harm in being immune to HIV?

jason0597• 5 years ago

I presume it would only be recommended for those who are sexually active (particularly homosexuals like me) and those who regularly use needles.

floatingatoll4• 5 years ago

Many who are 'sexually active' are also unwillingly so. By that criteria, it would be best to recommended it to all women and all prisoners in the United States, due to how common rape is among those populations here. I'd like to say "we are better as a society" but that's not true yet, and in the meantime, at least I won't have to worry about AIDS when it's my turn to be raped.

technofiend• 5 years ago

As with any vaccine the ideal outcome is the general population is vaccinated and we develop a herd immunity. For a deadly disease like HIV spending the effort to eradicate the disease would be for the best, but like HPV vaccination there's a moral judgment tied to it that will prevent some people from accepting everyone should be vaccinated.

FooBarBizBazz4• 5 years ago

As a side note, it was ridiculous that it took so long for boys to start getting the HPV vaccine. If you're a public health person, even if your only concern is cancer in women, you still want to vaccinate boys to improve herd immunity. If you're a heterosexual man, even if you only care about cancer in women, you would like to have been vaccinated if you are a remotely decent person, because you don't want to give women cancer -- especially the women you have sex with, who, generally, are going to be people you care about. And additionally there are male health concerns related to HPV -- for heterosexuals, primarily oral cancer, and for homosexuals, possibly also anal cancer (these being generalizations, of course). These are nasty, lethal diseases. Surely they should be prevented as well? Given the multitude of common-sense reasons to do it, for the benefit of so many people, it was frustrating to watch it happen only with such a long delay.

Much of the opposition seemed to come from a vengeful kind of religious conservative who wants sex to have negative consequences. Those conservatives represent a familiar kind of evil.

Yet I suspect that some opposition also came from women who had a problem with protecting men's sexual health. This is a newer kind of evil, and even less sensible for women who are heterosexual, for the herd-immunity reasons I outlined in my first paragraph.

A more-widely-administered HPV vaccine was literally a win-win for everyone, gay and straight, female and male, and still it came about slowly and faced opposition. This made me despair of my fellow humans.

hanniabu• 5 years ago

And then there's the new "muh freedom" crowd which will prevent any new mass vaccinations from becoming "mandatory" as we've done in the past.

paulydavis• 5 years ago

Africa really needs to be the target rollout for these vaccines if and when they materialize.

mxcrossb• 5 years ago

The Swazi population faces major health issues: HIV/AIDS and (to a lesser extent) tuberculosis are widespread.It is estimated that 26% of the adult population is HIV-positive. As of 2018, Eswatini has the 12th-lowest life expectancy in the world, at 58 years.

https://en.m.wikipedia.org/wiki/Eswatini

It seems countries like this could benefit massively from an effective vaccine

est313• 5 years ago

Africa really needs to be the target rollout for these vaccines if and when they materialize.

I'm not sure why this is downvoted. Africa is the most affected continent of the HIV pandemic.

Although the continent is home to about 15.2 percent of the world's population, more than two-thirds of the total infected worldwide – some 35 million people – were Africans, of whom 15 million have already died. Sub-Saharan Africa alone accounted for an estimated 69 percent of all people living with HIV and 70 percent of all AIDS deaths in 2011.

https://en.wikipedia.org/wiki/HIV/AIDS_in_Africa

colordrops• 5 years ago

Does this cure pre-existing infections

heavyset_go6• 5 years ago

The vaccines that I'm aware of only prevent infection in people without HIV. You can look up the vaccines on clinicaltrials.gov and find out their efficacy in different populations.

yarg2• 5 years ago

I'd guess so?

It seems to target cells outside of HIV's production pipeline (to stimulate them into becoming little antibody factories).

elil17• 5 years ago

At this point, no one knows if it actually prevents HIV, just that it produces a immune response (which can be detected through blood tests) which indicates that it could.

In general, it is possible that an HIV vaccine could lead to remission of pre-existing infections, but it's impossible to know yet if this one would do that.

ransom1538• 5 years ago

Dumb question: Isn't HIV a solved problem? With current anti-virals they can't even detect HIV in blood tests.

Daynil• 5 years ago

If you call requiring tens of thousands of dollars of maintenance medication treatment annually for life a solved problem, then absolutely!

SquareWheel2• 5 years ago

This still requires treatment for life, though. A vaccine would obviate this need, freeing up time, resources, and money for other healthcare.

eganist• 5 years ago

If there was a cost-effective cure, we could consider it solved. The only (functional) cure for it involves basically taking a sledgehammer to the entire immune system and replacing it with one from a donor with CCR-5 delta 32. As far as anyone's aware, this was only done with 2(?) patients who also had blood cancers.

Everyone else is popping antiviral cocktails and living with both the stigma of the disease and the risk of a relapse if they ever end up not being able to afford the drugs.

So... not quite solved. Hopefully this'll get us closer.

throw_m239339• 5 years ago

No it isn't. The costly treatment can have heavy side effects... for the people who can afford it, i.e. not most of people who are infected in Africa...

heavyset_go6• 5 years ago

Treatment is both expensive and taxing on the body, the drugs can cause renal problems and even renal failure. Multiple drugs need to be taken, they'll need to be switched up, and you'll need regular blood work to make sure that they aren't destroying your organs. You're going to need to see expensive specialists regularly for the rest of your life. You aren't going to only fill a prescription and take a pill and have that be the extent of your treatment.

There are several different and relatively large populations for whom complications can arise with treatment, like those with weakened immune systems, organ transplants, kidney disease, the elderly etc.

If you're wealthy and in otherwise good health, then yes, HIV is a relatively solved problem for you.

dennis_jeeves• 5 years ago

I'll answer the question to the best of what I know. It appears that there wasn't a problem to start with. Luc Montagnier, one of the co-discoverers of the AIDS virus for which he got the noble prize, is on record saying that it is a benign virus and in Africa at least is related to malnutrition. So unless the video is doctored one can take his word to be gospel. He is a heretic, btw.

Then there is Kary Mullis a noble prize winner (in chemistry) and the developer of the PCR test, who on investigation could not find any paper which indicated that the AIDS virus has been isolated, hence concluded that it's not proven that HIV causes AIDS ( or something to that effect).

If you cannot find the relevant videos on you tube search bitchute.

supernova87a• 5 years ago

From NPR interviews I listened to during the early days of the mRNA vaccines showing incredible promise, I understood that one of the problems with HIV is that the human body does not naturally have strong defense mechanisms (antibodies, etc) for this type of virus. Hence, the usual vaccine path (or mRNA derived method) of accelerating the learning of the body's T-cells, etc. to manufacture its own defenses is not very effective -- they are not there to begin with.

Is that not correct? What are they doing differently here?

est313• 5 years ago

Passive immunization with broadly neutralizing antibodies have been shown to prevent HIV infection in various animal studies. The goal is apparently to make the immune system able to manufacture such antibodies. The human immune system is fundamentally able to come up with these antibodies on its own, as some HIV positive individuals do develop them, but at least during natural infection they don't appear in everyone.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604566/

However, antibody levels won't be as high in vaccinated individuals as they are in those passive immunization animal studies, at least not forever. The body can't afford to produce full levels of antibodies for all antigens all the time. Instead, human bodies reduce produced antibody levels some time after the event that triggered the production of the antibodies. The immune system remembers the antibodies it has come up with, and can ramp up their production quickly if the antigen is re-encountered, but the question is whether this reaction is quick enough to prevent HIV infection. IIRC people with who produce broadly neutralizing antibodies naturally still eventually develop AIDS, if left untreated. Time has to tell if vaccinated individuals behave more like those animal models, or more like that subset of people who produce broadly neutralizing antibodies a few years post infection.

Until now, every vaccine for HIV has failed, and there have been many attempts. But you never win if you never try :).

xyzzy21• 5 years ago

We've been down this path before with vaccines. Often what seems promising early on doesn't pan out long-term.

This is why clinical trials are so lengthy. You have to operate at the time-constants of biology and the human body rather than political or business time-constants. The former are far longer than the latter.

BTW if you get a COVID vaccine right now, you are literally a clinical trial subject/participant. COVID vaccine clinical trials do not end until 2023 in the US based on FDA documents.

pfisch4• 5 years ago

List all the vaccines with negative long term side effects that don't appear within 4+ months.

astrange3• 5 years ago

Clinical trials for vaccines take a while because we don't intentionally infect people and it takes a long time for the test population to naturally catch whatever it is.

They went fast for COVID because it's a pandemic and everyone was getting it.

eli2• 5 years ago

Haven’t there been multiple HIV vaccines that cleared initial trials but did not actually work? Is antibody response rate a meaningful metric?

Phase 1 is only designed to test safety. This is great news, but way way too early to celebrate.

koheripbal• 5 years ago

The title seems to over-promise.

...the vaccine successfully stimulated the production of the rare immune cells needed to generate antibodies against HIV in 97 percent of participants.

This is not the same as creating a 97% antibody response.

The article goes on to say that it's part of a mutli-step process to create immunity, so it seems this initial shot is not enough.

This needs more clarity from someone with expertise in the field.

amluto• 5 years ago

Link with a bit more actual information: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5...

As far as I can tell, what's going on here is that there are multiple stages of antibody development. People have circulating B cells, and these cells have their genomes modified by the the VD(J) recombination process [0] from the genome in the human germline (i.e. what your germline cells and most of the non-B cells in your body have). There are a large number, but nowhere near infinite number, of B cells and corresponding antibodies that can be produced in this process, and I think these are what the authors call "germline" cells.

Once a naive B cell decides that it encodes a useful antibody (which is a complicated process), it starts to divide. Some of the daughter cells further mutate in a process called affinity maturation [1] to produce what are hopefully even better antibodies.

I think that the idea behind this research is that there are certain antibodies that can be produced by affinity maturation that are very useful against HIV, but that the "germline" B cells that lead to these antibodies are not particularly likely to be selected by the immune system when exposed to natural HIV antigens. Instead, the researchers have developed customized antigens intended to target specific germline cells which are known to be able to mature into cells that can produce the desired antibodies. If this works, the next step would be a series of additional vaccines (which are not the same as dose 1) that will try to encourage maturation into the useful antibodies.

The takeaway is that this result is very promising and that there is (so far?) no reason to expect the trial participants to be immune to HIV.

For the ML crowd, another way to think about this is that, when your body is exposed to an antigen, it runs a massively parallel search algorithm to find good antibodies in a truly massive space of possible antibodies. Unfortunately, most people, when exposed to real HIV or to prior vaccine attempts, get stuck in a bunch of not-fantastic local minima. The idea is to specifically aim the search in the right direction so, after a few rounds, it can find a better solution.

[0] https://en.wikipedia.org/wiki/V(D)J_recombination

[1] https://en.wikipedia.org/wiki/Affinity_maturation

laplacesdemon48• 5 years ago

Also from the Lancet link:

* VRC01 was shown around a decade ago to be one of several antibodies generated...that achieves broad neutralisation of several HIV strains

* 97% of participants who received an HIV vaccine immunogen candidate developed VRC01-class IgG B cells, precursors to broadly neutralising VRC01-class antibodies

* Results from another set of studies presented at HIVR4P (the Antibody Mediated Prevention [AMP] trials) showed that although intravenous administration of the VRC01 antibody at 8-week intervals did prevent infections with some strains of HIV, only 30% of the strains circulating in the trial regions of sub-Saharan Africa, South America, Switzerland, and the USA were sensitive to VRC01

To me this appears to be a great breakthrough but doesn't seem like a silver bullet.

ultimoo2• 5 years ago

I found that explainer at the bottom very helpful, thank you. (and I'm not even a part of the ML crowd!)

argonaut• 5 years ago

My understanding is that many HIV vaccine candidates have showed promising Phase I results but so far they have all failed in later trials.

https://en.wikipedia.org/wiki/HIV_vaccine_development lists five vaccines that made it to Phase 2-3 (and all failed). Two of them appeared to increase the risk of contracting HIV. The strongest candidate appears to have been ~30% effective.

djmips• 5 years ago

Interesting that there was some warnings given about using the same vectored technique on a Covid vaccine (AstraZeneca is an example) could also potentially increase the risk of contracting HIV? https://www.ajmc.com/view/researchers-warn-of-heightened-ris...

Note that Johnson & Johnson and AstraZeneca use different adenoviruses as vectors than Merck’s failed Ad5 vaccine.

New HIV vaccine with a 97% antibody response rate in phase I human trials

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