COVID: potential vaccine and med

I bring up these 2 snippets since they reflect the fact that there are lots of ongoing research efforts around the SARS-CoV-2 virus, and something is going to work (we live in hope, or at least try to ...). 

the first is about an interesting vaccine/delivery system (and is one of many different ongoing vaccine approaches), and th second is about the potential anti-SARS-CoV-2 effect of the old  antiparasitic drug invermectin.  Thanks to Julita Mir and Jon Pincus for sending these along

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Vaccine: There are many different types of vaccines being tried out for SARS-CoV-2 being developed. One interesting one that made it onto NPR involves a microneedle delivery system for a recombinant vaccine, from the University of Pittsburg School of Medicine. See https://www.pharmaexcipients.com/wp-content/uploads/2020/04/Microneedle-array-delivered-recombinant-coronavirus-vaccines.pdf

Details:

-- these researchers have been involved with vaccine development over years, specifically against the MERS-CoV virus. They targeted the spike protein, which is common to the SARS-CoV, the MERS-CoV, and now the SARS-CoV-2 virus, and seems to be crucial for viral transmission and infection by targeting the ACE2 receptor (which these coronaviruses bind to in order to gain host cell entry). for some of the studies on ACE2 receptors, see http://gmodestmedblogs.blogspot.com/2020/03/covid-ace2-ibuprofen-and-grasping-for.html and http://gmodestmedblogs.blogspot.com/2020/03/covid-ace2-more-info.html

-- for the MERS-CoV virus, they did develop a vaccine that elicited strong and long-lasting antigen-specific antibody responses evident as early as 2 weeks after immunization, as well as efficacious antibody-mediated neutralizing activity

-- within one month of the SARS-CoV-2 outbreak, they were able to design a specific vaccine for the new SARS-CoV-2 virus, based on the specific structure of the new virus and their previous research on MERS

-- they utilized a new vaccine delivery system: the dissolving microneedle arrays (MNAs: an injections techniques that delivers high concentrations of vaccines intradermally, to the local skin microenvironment, with minimal discomfort)

-- preliminary tests show that there was a potent antigen-specific antibody response in mice MNA-delivered SARS-CoV-2 vaccine

Commentary:

-- the MNA technology may well be important. studies with other viruses have suggested that intradermal vaccinations are more immunogenic leading to a higher antibody response vs traditional subcutaneous injections. Per their paper, “the skin has a rich population of antigen presenting and immune accessory cells capable of inducing a pro-inflammatory microenvironment favoring the induction of potent and durable adaptive immunity”

    -- I did see a study 25 years ago or so that found that hepatitis B vaccine, at 1/10 the dose (to my memory), elicited a profound antibody response in the host (this study came out when hepatitis B vaccine was relatively new and there were concerns about availability, especially in resource poor countries). The one negative was that there were more local reactions, likely related to its increased pro-inflammatory local effects. Subsequent articles have confirmed increased immunogenicity: eg see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484341/ or https://www.cdc.gov/flu/prevent/qa_intradermal-vaccine.htm or https://www.who.int/rabies/rabies_post_immunization/en/

So, still lots of work to be done. They need to test the immunogenicity of this (and all other vaccines) in humans, assess the actual induction of a neutralizing antibody response, see if this vaccine is in fact protective in animals, and, if all goes well, do human trials. Even the MERS-CoV vaccine, which was trialed in animals 10 years ago, was never approved for human use (it never spread the way our current iteration does).  many steps, any of which could go wrong...  but, there are so many different vaccines being developed, targeting different aspects of the virus, that hopefully one will be effective and safe. And, with this virus, it seems to me to be necessary to get a vaccine in order to prevent its continued ravages or likely recurrence (especially since there may be unquarantined asymptomatic/minimally symptomatic people). 

it will be hard to enforce and maintain virus control over many many months, relying only on largely voluntary restrictions on local and longer travel within the US, largely staying at home, many people may not able to have home-based jobs and therefore not working (with the attendant loss of income/health insurance), dealing with the myriad of adverse physical and mental health issues associated with decreased access to health care and likely increased issues of depression/isolation/domestic violence/suicide/etc/etc, and erosion of the important/necessary social interactions (Zoom only goes so far....)

in terms of domestic violence in the era of COVID-19, see https://www.unwomen.org/en/news/stories/2020/3/ending-violence-against-women-in-the-context-of-covid-19 , and https://www.nytimes.com/2020/03/23/opinion/covid-domestic-violence.html 

Ivermectin: A pre-publication study found that the long-standing, FDA-approved drug ivermectin inhibits the replication of SARS in vitro (see https://www.sciencedirect.com/science/article/pii/S0166354220302011 )

Details:

-- ivermectin, a very effective antiparasitic, does have anti-viral activity in vitro

    -- it has been shown to inhibit integrase protein and HIV-1 replication

    -- it also seems to limit infection by RNA viruses such as dengue, West Nile virus, Venezuelan equine encephalitis virus, and influenza; though no efficacy was found against the Zika virus in mice

        -- there was a phase 3 clinical trial of ivermectin for dengue in Thailand, finding that a single dose did not produce clinical benefit, though there were questions about the chosen dosage regimen

-- these researchers infected cells with SARS-CoV-2, added a single dose of ivermectin, and at 24 hours it was a 93% reduction in viral RNA present

-- at 48 hours the effect increased 5000 fold, “indicating that ivermectin treatment resulted in the effective loss of essentially all viral material by 48 hours”. No further change at 72 hours

So, maybe another possibility. Perhaps useful for preventing SARS-CoV-2 from infecting people in the first place. 

Again this is a medication that has been around for awhile, is FDA-approved, and is pretty safe/has minimal serious toxicity, both short and long-term (similar to chloroquine and hydroxychloroquine). These are huge pluses, given the unknown long-term toxicities of any new drugs, as well as some of the rarer shorter-term safety issues that might become apparent when many people get the drug. And, giving ivermectin at the same time might decrease the head louse and scabies populations (and ascaris, and pinworm, and Loa-Loa, and hookworm and.... the myriad of parasitic organisms that are susceptible).

geoff​

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