This is maybe better presented as Part 2b, since I covered the ‘minimum interval’ (or lack thereof) in Part 2. That dealt with the question about whether we need to separate different vaccines (eg. parvovirus abd rabies vaccines)by a minimum period if they aren’t given on the same day.

This post delves into the timing of boosters of the same vaccine.

Some vaccines are highly effective with a single dose. Our modified live vaccines are a good exmaple of that. If the animal is old enough to respond well (no maternal antibody interference), they just need a single dose. Other vaccines require a primer and a booster to get a good initial effect (e.g. leptospirosis, Lyme disease, feline leukemia). For those, an interval of 2-4 weeks after the first dose is commonly stated on the label.

Why 2-4 weeks?

It’s an interval that we know works and we aim for a short interval to get immunity ramped up ASAP. It doesn’t mean different intervals are necessarily ineffective. Companies aren’t going to test a wide range of different intervals for various reasons (e.g. it’s expensive, may require use of animals for challenge studies) so we don’t have clear guidance for what to do if we miss that recommended interval

Choosing timing of boosters requires us to think about how the immune system responds to serial doses of the same vaccine alongside our desire to get the animal well protected as soon as possible.

Longer than label intervals

This is related to Part 1 of this series…overdue animals. If we are starting a vaccine series and miss the recommended interval, that doesn’t mean we need to restart it. It just means we’ve been delayed in getting good protection since it took longer to get that key second dose.

So, if the dog got its first leptospirosis vaccine 6 weeks ago and hasn’t had a booster yet, I’d give the single booster dose now. The immune system hasn’t forgotten that primer dose and the booster will work fine.

In fact, longer intervals between vaccines can produce better immune responses. The sweet spot might actually be 3-6 months between doses, not 2-4 weeks. However, if we do that, it takes longer until the animal is protected. By boosting earlier, we maybe sacrifice the ultimate degree of protection a little to get the animal protected sooner. That’s a logical trade off.

The take home message is that if the label booster window for the initial doses was missed, just give the vaccine as if it came in on time.

Shorter than label intervals

Here, we get into some plausible concerns for which we have no data to support or refute. It’s also not really a yes/no issue. The immune system doesn’t suddenly change on day 14 after the first dose. It’s a continuum that we try to apply a specific breakpoint for. So, a couple days early probably means nothing. More than that raises some interesting questions.

Those relate to how the immune system responds to vaccines.

What we aim for is good production of antibodies in the short term AND establishment of a robust pool of cells that will be able to pump out more antibodies quickly if the animal is exposed to the pathogen (the boostable response). After vaccination, we get a nice initial antibody response from plasmablasts. Those are immature plasma cells and for them to help with longterm immunity, they have to mature into ‘adult’ plasma cells. This happens in germinal centres in lymph nodes, but those germinal centres take time to develop. A longterm response also requires establishment of T-helper cells, which help signal plasma cell production. That takes time to ramp up too. As a result, if a subsequent vaccine dose happens too soon, the vaccine response occurs independent of those germinal centres and with fewer helper T cells, and that can result in production of a lot more short term plasmablasts, not plasma cells (that pump out antibodies quickly in the future) and memory B-cells (that remember the antigen and help with a rapid response in the future).

The net result is that a very short interval might drive the response towards production of more short-lived plasmablasts and less maturation of the memory B-cell and long-live plasma cell responses that contribute to durable immunity. We get a nice blast of antibodies from that early second dose but maybe a less longlasting response.

Human rabies vaccination provides an interesting comparison. Post-exposure prophylaxis uses a series of rabies vaccine doses given over a short period (days 0, 3, 7 and 14) because the goal is rapid protection, with less concern about establishing longterm protection. We want lots of antibodies now to counter potential rabies exposure. In contrast, for routine rabies vaccination in people, vaccine is given on days 0 and no earlier than day 7, potentially with another dose at day 21 or 28. That’s to help develop longterm protection.

Let’s envision a scenario where a dog is due for its 2 week leptospirosis vaccine booster and it comes in early.

My first thought would be ‘can we get him back at the proper time?”. If that’s possible, let’s do that to stick with the label and not have to think more about the issues.

Sometimes that’s possible. Sometimes, we’re concerned that they won’t come back. It’s an extra step and extra hassle, and some people won’t do it. As I’ve said a few times, potentially suboptimal vaccination is usually better than no vaccination and I don’t want to pass up an opportunity to protect an animal.

Therefore, if I’m worried they won’t back, I’d think about the timing.

If it’s….

• 10-14 days after the first dose
  • That’s fine. A few days doesn’t likely make a difference. I’d have little concern.

• 7-10 days
  • That’s probably fine too. While we don’t have veterinary data, human vaccine schedules show that effective boosting can occur over that interval.

• Less than 7 days
  • Here, I’d be hesitant. There might be a good response, but I’d have less confidence that it would be a robust, longterm response that we want.
  • I wouldn’t give it, or if I absolutely had to, I’d consider it potentially ineffective and would want to give another dose later.
  • That would be a rare situation but if someone had a puppy that got a dose of leptpospirosis vaccine at 12 weeks and came in 6 days later because they were going camping today for a few weeks, I’d consider giving the 2^nd dose now (since the dog is probably not well protected and is potentially at high risk for exposure). I’d tell them that it’s a potentially effective dose for short term protection but I want to see them when they get back (at least 2 weeks after that dose) for another one before I’d be confident.

A lot of this is based on some best guesses and extrapolation. That’s always a challenge in veterinary medicine. We don’t often have directly relevant high level data to support important questions. In those situations, it’s important to look past habit or historical approaches, consider the evidence and make reasonable assessments based on current available evidence.