The scenario.

A dog is presented for vaccination, and DAPP (distemper, adenovirus, parvovirus), rabies and leptospirosis vaccines are recommended. After some discussion, the owner declines leptospirosis vaccination. The next day, she calls and says she’s read more about it and wants to get the dog vaccinated. When can she do that?

Often, I think people would say that the dog has to wait 2 weeks because that’s the minimum interval between vaccines?

There is no clear immunological basis for a universal 14-day minimum interval between vaccines in dogs and cats. There are some potential concerns about certain types of vaccines, which I’ll discuss below, but there is no evidence that this applies to the vaccines we routinely administer or that it results in clinically important vaccine failure.

Yet, it’s a pretty well entrenched dogma. It’s been propagated through teaching, continuing education talks and reviews for years, but if you try to trace back the recommendation, you eventually hit a dead end. There’s no scientific foundation.

If we look at possible concerns and mechanisms, nothing plausible comes up. It gets stated that the immune system can get overwhelmed or overloaded, but there’s no evidence that happens. We get bombarded by antigenic stimuli every day. Our immune systems are designed to be ready to go 24/7.

If we look to human medicine (which we do a lot because they typically have a lot more data), there’s no recommendation to have a minimum duration between most vaccines, and the exceptions don’t apply to our vaccines.

CDC’s guidance for timing of different vaccines says “There is no evidence that non-live vaccines interfere with the immune response to other non-live vaccines or to live vaccines. Any non-live vaccine can be administered either simultaneously or at any time before or after a different non-live vaccine or live vaccine. The 2 exceptions are a 4-week interval between PCV13 and MenACWY-D in a person with anatomic asplenia and the separation of doses between PCV13 and PPSV23. Limited data are available regarding interference between live vaccines used in the United States. The immune response to one live-virus vaccine might be impaired if administered within 28 days (i.e., 4 weeks) of another live-virus vaccine. In a study conducted in 2 U.S. health maintenance organizations, the risk for varicella vaccine failure (i.e., varicella disease in a vaccinated person) among persons who received varicella vaccine within 28 days of MMR vaccination was threefold higher than among persons who received varicella vaccine >28 days after MMR vaccination. Another study determined that the response to yellow fever vaccine is not affected by monovalent measles vaccine administered 1–27 days earlier. The effect of nonsimultaneous administration of rubella, mumps, varicella, and yellow fever vaccines is unknown.”

So, for injectable vaccines, the concern is only when there’s serial administration of two modified live vaccines, and likely only certain modified live vaccines, not all of them. We have modified live core (DAPP for dogs, FVRCP for cats) vaccines, but the other vaccines we use (leptospirosis, rabies, Lyme disease, feline leukemia) are non-live vaccines. There are some live feline chlamydia vaccines but those are typically part of FVRCP vaccines. If there was a chlamydia-only live vaccine somewhere, I’d consider spacing it by 4 weeks from core vaccines, but we don’t know if that’s necessary. Beyond that, we don’t have the potential for giving different modified live vaccines over a short interval since we don’t have different modified live vaccines to give.

For the scenario above, my answer is “vaccinate it anytime. There’s no concern.” I don’t want to miss an opportunity to vaccinate. It’s not uncommon to hear stories about situations akin to scenario 1 where they were told to wait a few weeks before they can get the vaccine, and they never book the later appointment.

That’s focused on injectable vaccines, so let’s switch up our scenario.

A dog is presented for vaccination, and gets DAPP (distemper, adenovirus, parvovirus), rabie, and leptospirosis vaccines are recommended. The next day, the owner calls and says they will be boarding the dog later this year and want to get a kennel cough vaccine. You recommend a mucosal (oral or intranasal) vaccine since they are more effective than injectable kennel cough vaccines. When can you give that?

I think we’ve often ignored mucosal vaccines when thinking about the ‘minimum interval’ and this may be the scenario where it’s actually relevant. Mucosal (oral, nasal) vaccines that we use for kennel cough (Bordetella bronchiseptica, canine parainfluenza virus, adenovirus) are live vaccines and there might be some issues to consider, but we have a complete lack of data.

For humans, CDC says “Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 4 weeks, to minimize the potential risk for interference. If 2 such vaccines are separated by <4 weeks, the second vaccine administered should not be counted and the dose should be repeated at least 4 weeks later. On the day a live injectable or intranasal vaccine will be administered, providers should ensure that no live injectable or intranasal vaccine was given in the previous 28 days.”

This is the one situation where there might be a biologically plausible argument for a minimum interval. Whether it actually matters clinically is another question. We have no idea if it’s an issue for our patients, but this is the scenario where we have potential concerns if a live core vaccine and live intranasal or oral vaccine are given less than 4 weeks apart.

Honestly, I’ve never really considered this to be a big concern, and I’ve been more concerned about missing an opportunity to protect against a vaccine-preventable disease. I don’t think we can ignore it completely, though.

So, in our scenario, I’d consider how important the vaccine, both in the very short term and over months. We could recommend waiting 4 weeks for the kennel cough vaccine out of abundance of caution. However, if the dog was imminently going to a high risk situation (e.g. boarding) very soon and the wait might pose undue risk, I’d give the vaccine, but would recommend giving another dose 4 weeks later given the theoretical potential for a poorer response. If the timeframe is longer, whereby they won’t really need that protection for a few months (e.g. it’s September and they’re going to be boarding over Christmas), it’s easier to delay.

Is that overkill? Maybe. (Probably?) But, it’s the one situation where the most plausible basis to requiring a minimum dosing interval.

The bottom line…. There is no evidence supporting a 14-day minimum interval between all vaccines in dogs and cats. For non-live vaccines, (rabies, leptospirosis, Lyme disease, FeLV), there is no realistic basis for a minimum interval. The only scenario where a minimum interval could plausibly matter is sequential administration of two live vaccines, which is not something that would be regularly considered, and even there it’s based on extrapolation, not evidence demonstrating clinically important interference in dogs or cats.

That also raises questions about vaccination in shelters. Shelters often used frequent vaccination with live vaccines, and give kennel cough vaccines to dogs as part of that. Are we vaccinating suboptimally in some situations, or is this the natural experimental model that shows we maybe don’t have concerns? Those are interesting discussion points but  shelter approaches to vaccination are probably fodder for a separate post.