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Intramuscular vaccinations are the most important first step and will keep hospitalization down. But intramuscular vaccination for respiratory viruses does not

Intramuscular vaccinations are the most important first step and will keep hospitalization down. But intramuscular vaccination for respiratory viruses does not provide long lasting immunity to the surface mucosa tissues of the upper respiratory tract. The IgG antibodies in body serum do seep into the lower lungs and provide robust protection from serious disease, but they do not prevent infections very long in the nose, sinuses, or throat. This is the disparity many studies are now highlighting but failing to acknowledge the cause of. The required next step is intranasal vaccination to recruit B and T cells to the upper respiratory mucosa and have the B cells produce local IgA antibodies. This would actually stop infections (infections defined from nasal swab testing). It is up to the NIH and other large organizations in the world to get this messaging out there. There are two types of "breakthrough". There's the fact that intramuscular vaccinations don't protect the upper respiratory mucosa, and then there's the very rare cases when sars-cov-2 actually manages to infect body organs and the lower lungs. They are entirely different things. The variants currently circulating don't play a huge role in this discrepancy. We'd be seeing the same amount of upper respiratory mucosa infections (not hospitalizations) even if there were no delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2. ref: https://www.gov.uk/government/publications/long-term-evolution-of-sars-cov-2-26-july-2021 https://www.gov.uk/government/publications/long-term-evoluti... page 5, #8. "Whilst we feel that current vaccines are excellent for reducing the risk of hospital admission and disease, we propose that research be focused on vaccines that also induce high and durable levels of mucosal immunity in order to reduce infection of and transmission from vaccinated individuals. This could also reduce the possibility of variant selection in vaccinated individuals." ref: https://science.sciencemag.org/content/373/6553/397 https://science.sciencemag.org/content/373/6553/397 "the ideal vaccination strategy may use an intramuscular vaccine to elicit a long-lived systemic IgG response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including IgA secretion and tissue-resident memory cells in the respiratory tract." ref: https://www.nature.com/articles/s41577-021-00550-x https://www.nature.com/articles/s41577-021-00550-x

UncleOxidant 5y ago
Why isn't there more of a push for emergency use of intranasal vaccines? Apparently there are some in the testing phase, but I think if they were given as much resources as the mRNA vaccines were we might have already had an intranasal vaccine in use by now. The Israelis have one in testing but it still sounds like it's a long ways off from being deployed on a large scale. The other advantage of an intransal vaccine is that we might be able to convince a portion of the vaccine hesitant to get it.
- rolph 5y ago
  nasal mucosal immunity[IgA] is short term relative to humoral immunity[IgG; IgM]; this however would be a good prophylactic approach, as the nasal vault is a major contributor to transmission mechanisms
  - superkuh 5y ago
    Yes, the neutralizing antibodies go away relatively quickly but now you have mucosal resident T cells trained on spike epitopes ready to go right at the start of the infection before things get out of hand.
- Animats 5y ago
  Here's a good explanation of why.[1] There are several intranasal coronavirus vaccines in test. There's only one approved nasal vaccine now, for anything: FluMist. It's not recommended for people over 50. There have been previous failures. Intranasal vaccines are hard to make work. Think of the current mRNA vaccines as a minimum viable product. The basic formulation was computed days after the virus was sequenced and they made it to market fast. They do the basic job. Serious side effects are rare. They require two doses and later, boosters. They're a pain to store and ship because of cold requirements. They're hard to manufacture because putting fragile messenger RNA into a liquid carrier envelope requires exotic equipment. They have reduced effectiveness for virus variants. Expect later-generation products that solve some of those problems. [1] https://www.pbs.org/newshour/health/scientists-debate-potential-benefits-of-intranasal-covid-19-vaccines https://www.pbs.org/newshour/health/scientists-debate-potent...

UncleOxidant 5y ago

Why isn't there more of a push for emergency use of intranasal vaccines? Apparently there are some in the testing phase, but I think if they were given as much resources as the mRNA vaccines were we might have already had an intranasal vaccine in use by now. The Israelis have one in testing but it still sounds like it's a long ways off from being deployed on a large scale. The other advantage of an intransal vaccine is that we might be able to convince a portion of the vaccine hesitant to get it.

rolph 5y ago
nasal mucosal immunity[IgA] is short term relative to humoral immunity[IgG; IgM]; this however would be a good prophylactic approach, as the nasal vault is a major contributor to transmission mechanisms
- superkuh 5y ago
  Yes, the neutralizing antibodies go away relatively quickly but now you have mucosal resident T cells trained on spike epitopes ready to go right at the start of the infection before things get out of hand.
Animats 5y ago
Here's a good explanation of why.[1] There are several intranasal coronavirus vaccines in test. There's only one approved nasal vaccine now, for anything: FluMist. It's not recommended for people over 50. There have been previous failures. Intranasal vaccines are hard to make work. Think of the current mRNA vaccines as a minimum viable product. The basic formulation was computed days after the virus was sequenced and they made it to market fast. They do the basic job. Serious side effects are rare. They require two doses and later, boosters. They're a pain to store and ship because of cold requirements. They're hard to manufacture because putting fragile messenger RNA into a liquid carrier envelope requires exotic equipment. They have reduced effectiveness for virus variants. Expect later-generation products that solve some of those problems. [1] https://www.pbs.org/newshour/health/scientists-debate-potential-benefits-of-intranasal-covid-19-vaccines https://www.pbs.org/newshour/health/scientists-debate-potent...