Why can't vaccines be injected directly into the blood?

[Green Xenon]

Hi:

 

Vaccines are usually given via intramuscular injection. What are the risks if they are given intravenously instead?

 

 

Thanks,

 

Green Xenon

[GDG]

Basically, you want the vaccine antigens to be washed into the lymphatic system, and taken up by dendritic cells. Much greater chance of that happening if you inject into the muscle. If injected IV, chances are that the antigens will be dispersed, and you won't have a concentration high enough to activate the immune system at any location.

[jimmydasaint]

GDG, can you please back up your statement with an appropriate reference. IMHO, both routes are effective at inducing immune responses, although the IV route is faster. IMHO, again, the intramuscular injections are easier and have become established custom and practice.

[GDG]

My recollection is from an immunology course, years ago. The only text I have at hand is James W. Goding, "Monoclonal Antibodies: Principles and Practice" (1983 Academic Press) which states that

"The first injection of antigen should be given in a highly aggregated form, because soluble monomeric proteins in their native state are poorly immunogenic and tend to induce tolerance (Dresser, 1962) [D.W. Dresser, Immunology (1962) 5:378-88]."

(Goding at p. 58.)

 

On reflection, anything in the blood will eventually end up in the spleen or lymphatic system anyway...

[jimmydasaint]

Thanks for that answer GDG. I don't think, IMO, that many researchers or clinicians would ever administer soluble antigens without a suitable immunopotentiator- for example Freunds adjuvant, IIRC. And yes, it would make sense that the lymphatics will present antigens suitably to the specific arm of the immune system.

 

However the other advantage of intramuscular injection, apart from slower, more gradual delivery of the suitable chemical, is that it can be administered far more easily to a patient in any position without having to turn the patient around for suitable large veins.

 

I have found some advantages and disadvantages below:

INTRAMUSCULAR INJECTION Self-Directed Learning Package Developed by Thunder Bay Base Hospital Program Fall 2008 CME Intramuscular Injection Self Directed Learning Package

 

Advantages of Intramuscular Injections: 1. Medications are completely absorbed. 2. Absorption is quicker than subcutaneous route due to increased vascularisation. 3. IM is a safer technique to use on thin patients. 4. IM is a safer technique to use with an agitated or combative patient. Disadvantages of Intramuscular Injections: 1. There is increased discomfort with an intramuscular injection if poor technique is used. 2. There is a risk of hitting a nerve, causing nerve damage. 3. There is a risk that an abscess may form at the injection site

http://www.tbrhsc.net/clinical_partners/base_hospital/cme/2008%20IM%20Study%20Guide.pdf

[GDG]

Well, a clinician will not be using Freund's: not approved for use in humans, and fairly nasty stuff. To quote Goding again:

"Freund's adjuvant should be prepared with care. Accidental injection into the hand may result in permanently stiff or useless fingers, and hypersensitivity reactions can be very severe (Chapel and August, 1976) [H.M. Chapel & P.J. August, Clin Exp Immunol (1976) 24:538-41]. Glass syringes are recommended because the plunger of plastic disposable syringes tends to swell and stiffen in oil. Failure to use Luer-lock fittings will usually result in the couplings coming undone, and the resultant widespread spraying of adjuvant may cause permanent eye damage."

James W. Goding, "Monoclonal Antibodies: Principles and Practice" (1983 Academic Press) at p. 59.

[jimmydasaint]

My mistake about Freunds but in humans the original point still stands - soluble antigens are unlikely to be used for immunogenic responses in experimental animals, or humans, without immunopotentiators. In humans, I am not sure what is used as a carrier - is it Aluminium salts?

 

Yes just found this:

Aluminium compounds have been used as adjuvants in practical vaccination for more than 60 years to induce an early, an efficient and a long lasting protective immunity and are at present the most widely used adjuvants in both veterinary and human vaccines. Although the last two decades of systematic research into the nature of these adjuvants has contributed significantly to understanding their nature and their limitations as Th2 stimulators the more detailed mode of action of these adjuvants is still not completely understood. We have a comprehensive record of their behaviour and performance in practical vaccination, but an empirical approach to optimising their use in new vaccine formulations is still to some extent a necessity. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

http://www.ncbi.nlm.nih.gov/pubmed/15315845?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedreviews&logdbfrom=pubmed Edited July 25, 2009 by jimmydasaint

[Maneco]

Hi to all.

The topic question was "Why can't vaccines be injected directly into the blood?" and the discussion derived to another theme.

I came here looking for "what happens if an i.m. vaccine e.g. Recombinant Hep-B vaccine is administered i.v. instead?".

Difficult to find information about.

Thanks to all.

[StringJunky]

To maximize efficacy you want to  create an 'infection' site where the antigen signal from the vaccine is concentrated enough for long enough to initiate an immune response. If you applied it IV the standard vaccine dose will be diluted too quickly. You could increase the dose for it to work but that would increase the chance of an adverse event and make it unnecessarily expensive. In short, the vaccine concentration will dilute too quickly doing it IV. 

Edited October 27, 2018 by StringJunky

[PhilGeis]

Adjuvants are commonly used with a number of vaccines.  https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html  and https://www.fda.gov/ScienceResearch/AboutScienceResearchatFDA/ucm552882.htm

[mistermack]

I wondered if the more sudden delivery of the vaccine in the blood system might be more likely to trigger an allergic reaction. I'm sure that would have been investigated a long time ago, but I don't know what the answer is. 

If it was the case, I suppose the advice would be to deliberately avoid a blood vessel. Don't know if that's the case either.

[Maneco]

No, it wasn´t exactly that but..

The young nurse has administered the vaccine i.v. instead of i.m. ...

[CharonY]

On 10/27/2018 at 3:22 AM, StringJunky said:

To maximize efficacy you want to  create an 'infection' site where the antigen signal from the vaccine is concentrated enough for long enough to initiate an immune response. If you applied it IV the standard vaccine dose will be diluted too quickly. You could increase the dose for it to work but that would increase the chance of an adverse event and make it unnecessarily expensive. In short, the vaccine concentration will dilute too quickly doing it IV. 

The interesting bit is that while the depot effect was assumed to be true, there actually has not been any systematic study on depot effects (and as Phil mentioned, adjuvants are now routinely used). Rather since the development was rather early on already focused on intramuscular (or subcutaneous) injections and shown to be effective at that, that intravenous injection never really became relevant. As such there were at best only case studies of accidental IV injection, but really no systematic investigation of possible issues.