Earlier this week (in part 2 of this series) I covered minimal intervals for giving pets different vaccines (when they’re not given on the same day). This post will cover intervals for giving boosters of the same vaccine, particularly in pets being vaccinated for the first time (I covered boosters for overdue pets in part 1).
Some vaccines, such as our core modified live vaccines for dogs and cats, are highly effective even with just one dose. That means if an animal is healthy and old enough to no longer have circulating maternal antibodies (which can interfere vaccine response), it really only needs one dose of vaccine, not a series. Other vaccines (e.g. leptospirosis, Lyme disease, feline leukemia) require a “primer” and a “booster” dose to achieve an effective response; the label recommendation for these is typically to give the booster 2-4 weeks after the first dose.
We use a 2-4 week interval because we know it’s long enough to work as a booster, but also relatively short so the animal is protected as soon as possible; however, that doesn’t mean that a different interval won’t also work. The vaccine manufacturers don’t test how well their vaccines work at a whole bunch of different intervals (as it’s expensive and requires more animals to do more challenge trials), so we don’t have clear data on what happens if we miss the recommended booster interval. To make a decision in these cases, we need to consider how the immune system responds to serial doses of the same vaccine.
Longer than label booster intervals
If we are starting a vaccine series and miss the recommended interval, that doesn’t mean we need to restart it. It just means the animal was not protected as soon as it could have been, since it took longer to get that important second dose.
- If an adult dog got its first leptospirosis vaccine, missed the booster at 4 weeks and instead came in 6 weeks after the first dose, it can just have a single booster now without having to “restart the series.” The immune system hasn’t forgotten the primer dose, and the booster will work fine. For further discussion and details, see the part 1 post from earlier this week on overdue pets.
A longer interval between boosters may actually produce an even better immune response in some cases. The best interval to use for this may actually be 3-6 months, not 2-4 weeks, but that would mean the animal in question isn’t fully protected for a lot longer. By boosting earlier, we might be sacrificing a little bit in terms of the maximum degree of protection, but we get the animal protected sooner, which is a logical trade (and remember that the 2-4 week interval has been tested by the vaccine manufacturer so we know it works well enough).
The take home message is not to get hung up on a 2-4 week vaccine series, as long as the animal gets that all-important booster (and the sooner it gets it thereafter, the sooner it’s protected).
Shorter than label booster intervals
There are some plausible concerns with shorter intervals, but unfortunately we have no data to either support or refute them. There’s also lots of grey, because the immune system doesn’t suddenly change on day 14 after the first dose of a vaccine. The immune response is on a continuum to which we are trying to apply a specific breakpoint that will work for most of the population. So a booster on day 12 or 13 likely isn’t a big deal, but an even shorter interval could be problematic because of the the way the immune system responds and creates memory. Following vaccination, we want the body to produce antibodies in the short term for immediate protection, AND establish a robust pool of immune cells that will be able to quickly ramp up antibody production again in the future on subsequent exposure to the pathogen (or a booster vaccine).
- Antibodies are initially produced by immature plasma cells (plasmablasts). For long term immunity, the plasmablasts need to mature into “adult” plasma cells in germinal centres in the lymph nodes, and there also needs to be a population of specific T-helper lymphocytes that help signal plasma cell production. That all takes time. If a booster vaccine is given too soon in the process, the response occurs without the help of those germinal centres and with fewer helper T cells, so instead of producing plasma cells and memory B-cells (that help produce durable immunity with rapid response in the future), the response just produces more short term plasmablasts.
Pre- and post-exposure rabies vaccination in people provides an interesting comparison. After a rabies exposure, a person is given a series of vaccine doses over a very short period (days 0, 3, 7 and 14) because the main goal is rapid immediate protection (to intercept any virus already in the body), not establishing long term protection against future exposures (but there will still be some, of course). For pre-exposure rabies vaccination in people, the first two doses are given no less than 7 days apart, with another dose usually between day 21 or 28 from the first dose, which is the more effective strategy for establishing long term protection.
Picture this: A dog is due for its leptospirosis vaccine booster at two weeks, but it comes in early. Do you give it the booster, or tell the owner to come back at the two week mark?
- If it’s possible to have the dog come back, that would be ideal, so we’re following the label instructions and don’t need to think about the other issues.
- Sometimes we’re concerned that the owner won’t bring the dog back because it’s too much hassle. Potentially suboptimal vaccination is usually better than no vaccination, and I don’t want to pass up an opportunity to protect an animal, so if that’s the case consider how early might be too early:
- 10-14 days after the first dose: Likely won’t make a big difference. I’d have little concern with giving the booster right away.
- 7-10 days after the first dose: Probably also fine. While we don’t have veterinary data, human vaccine schedules show that effective boosting can occur over this interval.
- Less than 7 days after the first dose: Questionable. The animal may still have a good short term response, but may not develop robust, long term immunity. If two doses are inadvertently given this close together, I’d consider the second dose potentially ineffective and recommend an additional booster at least two weeks later. The rare situation where it might be worthwhile to booster right away is if someone had a puppy that got a dose of leptospirosis vaccine at 12 weeks of age and came in 6 days later because they were going camping today for a few weeks. I’d consider giving the puppy the booster then (to try to give the dog more short term immunity for the camping trip when it’s at high risk of exposure), but I’d recommend a third dose later on to be confident in the long term protection.
I admit that a lot of this is based on some best guesses and extrapolation. As is often a challenge in veterinary medicine, we don’t often have directly relevant high level data to help guide us in these situations. Nonetheless, it’s important to reassess old habits and historical approaches and consider what evidence and data we do have, to help us make the best decisions we can.