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Moderna’s HIV vaccine has officially begun human trials

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Re: Moderna’s HIV vaccine has officially begun human trials

#241

Post by tylerhou »

ifyoubuildit wrote: post #169
joshuamorton wrote: post #145

Earlier quoted context omitted.

> But if I told someone that I don't need to know the effects of v7.1.3 before patching it because I can't think of a mechanism for it going wrong, and besides, we already released all those other versions and they were fine, I'd hopefully be fired. But this isn't what they're saying. They're saying that there are few to no ways for it to not have any detectable issues for 6 months and then suddenly go wrong (which I…

> But this isn't what they're saying. They're saying that there are few to no ways for it to not have any detectable issues for 6 months and then suddenly go wrong (which I'll note is also true for software!). Over the years I've become a little obsessed with imagining the ways things can fail (I'm just as fun at parties as you can probably imagine). An example that immediately jumps to mind where that is not true fo…

Let's suppose that your software currently has an incident where the service is degraded. For every day you don't push a fix, you lose 0.X% of revenue.

Some engineer creates a fix by turning off some recently added experiment responsible for the service degradation. The rollback passes all unit tests and integration tests. You know this fix is low-risk (maybe because your service was healthy for the ~1 year prior to the rollout). Even if there is some risk that this rollback breaks the service at some point in the future, in comparison to the known revenue loss the expected loss of that breakage would be minimal.

Another engineer objects to the rollback saying that "they don't know of the long term effects of such a rollback." You try to counter their claims by showing that previous rollbacks were almost always successful, and when they caused another failure that failure was not nearly as bad as the original service degradation. Also, the rollback passes all tests. That engineer then repeats "we don't know of the long term effects of this particular rollback, and I'm skeptical that the fix is good because the failing experiment and rollback was identified so quickly."

(Rollback vs. fix-forward doesn't actually matter; the point is that all available knowledge shows that the fix is low risk, historically supported, and that there is likely no mechanism for random failure in 6+ months.)

Do you think it would be correct to prefer the second engineer's claims?

Re: Moderna’s HIV vaccine has officially begun human trials

#242

Post by balaji1 »

hn_throwaway_99 wrote: post #10

As I understand it, the reason an HIV vaccine has been so difficult to create is that HIV mutates so easily. I understand the basics behind how mRNA vaccines are generated, but I don't understand why this approach would be expected to have any more success in evading the high mutation potential of HIV than other vaccine types. After all, it was even a concern with new coronavirus variants that the original Moderna va…

so everybody gets it soon?

Re: Moderna’s HIV vaccine has officially begun human trials

#243

Post by abletonlive »

thebradbain wrote: post #154
hn_throwaway_99 wrote: post #10

As I understand it, the reason an HIV vaccine has been so difficult to create is that HIV mutates so easily. I understand the basics behind how mRNA vaccines are generated, but I don't understand why this approach would be expected to have any more success in evading the high mutation potential of HIV than other vaccine types. After all, it was even a concern with new coronavirus variants that the original Moderna va…

I’m not a doctor, but as a gay man: it’s my understanding HIV doesn’t mutate in the same way a disease like Covid does, at least not in the sense that there’s as many opportunities to spread (i.e. not airborne), so while HIV may actually mutate more in theory, it gets less chances to spread, so less completely-different variants become widespread. Also, as part of “stopping the spread” PrEP has existed for years. It’…

>I honestly don’t know why everyone who is sexually active isn’t on PrEP

Side effects. People generally don't like to take drugs to prevent things if the chances of acquiring the illness is minimal. For example, if we had an approved vaccine for Malaria, we wouldn't just give it to everybody in the USA, and even if we did, many would not take it.

Re: Moderna’s HIV vaccine has officially begun human trials

#244

Post by mlyle »

stjohnswarts wrote: post #229
chucksmash wrote: post #186

Earlier quoted context omitted.

Presumably the viral load required for transmission is greater than the viral load required for detection.

That seems like a big if? maybe 0.5% of people actually are succeptable to the lowered viral load. Have studies been done that would detect such a population?

One reason we believe this is that we can typically detect virus quantities way too small to reliably replicate in culture, and believe that in vivo infection is even harder than in culture (because of innate immune response and the body not being composed just of the most susceptible cells).

You generally can't measure infectious dose directly without a highly unethical challenge study. You can sometimes know concentrations that did or didn't result in infection in various real world scenarios, and sometimes you have circumstantial evidence (e.g. you can know how much virus a person sheds, and what proportion of a room with certain ventilation quantities got infected).

Re: Moderna’s HIV vaccine has officially begun human trials

#246

Post by khazhoux »

somesanityplz wrote: post #165
khazhoux wrote: post #155

Earlier quoted context omitted.

But see, you didn't actually make a point in your original comment. I don't mean that rudely. You referred to the "arrogance [we] likely use to discuss the correctness of [our] code." What are actually saying here? If you want to engage in discussion, I encourage you to use plain language. Accuse the community directly of whatever charge you're bringing, and then we can debate.

Would you deploy in production a software (which lack of safety could be critical) without being sure (or have proof) if it will effectively work as expected in 1+ years? Would you be relaxed being the administrator of such a software?

All the manners in which the vaccine could have been tested, were employed before deployment. The only thing that wasn't done, as you note, is to wait for XX number of years to see long-term side effects. So in fact, we don't know what the effects of this vaccine will be in 10 years -- because the only way to know that is to wait 10 years. But... there is also no indication, from similar vaccines, that "something terrible" happens in 10 years.

A lot of people out there are just imagining, out of nowhere, than in 10 or 20 years, everyone who got the vaccine is gonna get autism or sprout a third nipple or keel over dead. But they're just imagining this. I can imagine a lot of things too... like, who here can prove to me that the new Doritos flavor introduced last year won't trigger brain cancer in 20 years? Anyone??

Re: Moderna’s HIV vaccine has officially begun human trials

#248

Post by mlyle »

siver_john wrote: post #218
mlyle wrote: post #62

Earlier quoted context omitted.

> this approach is moved to human trials where others have not, I can only conjecture. Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). They early ones showed no efficacy; the newer ones we just don't know (yet). The main benefit of mRNA is iteration: you can try a whole lot of different protein mixes and see what works best in an animal model. A seconda…

>Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. But thanks for the clarification. And the mention of viral vectors which are an area I was less aware of till recently but it has been cool t…

> I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA.

Yes, and one vaccine approach is getting a bacterium or other virus to make a lot of a protein you're interested in, and then purifying the stuff you're interested in and forming it into a vaccine product. These are recombinant approaches. E.g. https://en.wikipedia.org/wiki/AIDSVAX is exactly what you describe: a viral protein vaccine developed using recombinant approaches from e.g. Chinese hamster ovary cells https://pubmed.ncbi.nlm.nih.gov/8142140/

The first was a hepatitis B vaccine developed in the 1970s where yeast cells were modified to make hepatitis B proteins. Then the HPV vaccine used the same approach, choosing proteins that would spontaneously assemble into a virus-like particle that triggers a strong immune response.

Complicated proteins have to come from a living thing, in practice. So if you're going to administer a viral protein, it has to come from purifying virus that you've grown or from a recombinant approach of some kind (and growing HIV is problematic for multiple reasons).

Re: Moderna’s HIV vaccine has officially begun human trials

#249

Post by jl6 »

lixtra wrote: post #239
jl6 wrote: post #232

Earlier quoted context omitted.

It does sound suspiciously like wishful thinking though, doesn’t it? You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted, and of course they are going to look like a “no transmission” case if you lack the ability to detect that amount of virus. And that’s either not a problem (if trace levels = no symptoms), or a ticking time bomb w…

> You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted… You don’t need to be a 100% sure. Once the risk becomes small enough you can spend your time worrying about other risks.

Now that may be entirely the right posture, but the triple equals signs in the post upthread did rather imply certainty.
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