NEW! Veterinarian’s Corner: MLV and Killed Vaccines – Dr. Chris Chase, South Dakota State University

By Dr. Chris Chase, South Dakota State University Department of Veterinary and Biomedical Sciences

In the last 40 years, we have seen several waves in which type of vaccine – modified live vaccines (MLV) or inactivated (killed) – is the most efficacious and safe.

Safety issues accompanied MLV when they were first introduced in the ’70s and ’80s.  Inactivated vaccines were seen as safer, but not quite as efficacious.  In the ’90s and early 2000s, MLV vaccines were perceived to have become safer and their efficacy was superior to the old alum inactivated vaccines.

Beginning in the late ’90s, changes were made to improve the efficacy of inactivated vaccines.  Much of this improvement was driven by improved adjuvants.  Adjuvants are the mixtures of molecules added to vaccines to make the immunity better and make the immune system work more efficiently to provide longer immunity (duration of protection).  The discovery and development of better adjuvants was helped considerably by the research to develop HIV-AIDS vaccines.  Although no human HIV-AIDS vaccine has been licensed to this day, the work on adjuvants has made animal vaccines much better.

Together may be better
Beginning in the 2000s, we had evidence that using inactivated vaccines as boosters for animals vaccinated with MLV resulted in higher antibody responses and good cell immunity.  This increase in antibodies is really important for the formation of colostrum by dry cows, since almost all of the antibodies in colostrum comes from the serum of the animal.

We also had evidence that two doses of inactivated infectious bovine rhinotracheitis (IBR) vaccine could protect against abortion.  However, two doses of inactivated vaccines for bovine viral diarrhea virus (BVDV) and persistent infection (PI) wasn’t quite as good as MLV.  Recently, a three-year study showed animals vaccinated with MLV first and then boosted with inactivated vaccine had fewer BVDV PIs and fewer IBR abortions than animals vaccinated and boosted with only MLV.

Active immunity:  A problem for MLV
One of the issues with a “well-vaccinated animal” is that its immune system has been trained to eliminate the virus or the bacteria.  The problem is the immune system can’t tell the difference between the vaccine strain and the field or wild strain.  We can’t expect an animal repeatedly vaccinated with MLV will be boosted.  For an MLV to work, the vaccine organism has to grow to a sufficient level to fully activate all the steps needed for a vaccine response. When the active immunity stops the vaccine organism from growing, the full response can’t happen.

This is also an issue we face with maternal interference, which is when colostral antibodies from the cow “interfere” with the vaccine.  The only difference is that maternal antibodies decay or disappear with time.  That’s not so with active immunity as these antibodies and immunity are produced by the animal and are there for a lifetime.

The problem is the label
Many of the studies that have demonstrated MLV and inactivated vaccines working together have been done where the animals were given two or three MLV vaccinations followed by a single inactivated vaccine.  In the U.S., the labels for inactivated vaccines for cattle all require two doses.  That means giving a single dose as a booster is “off label.”  Swine vaccines do have a single dose label for some inactivated vaccines, but I have not seen any USDA label for an MLV-inactivated combination.  These types of labels do exist in Europe.

Going forward
We are beginning to see some safety issues with MLV vaccines, particularly related to IBR.  At the SDSU Diagnostic Laboratory, we have been sequencing the IBR abortion viruses since 2009 and all the viruses isolated appear to be vaccine viruses.  Some work has also shown a 6- to 8-percent reduction in first service conception in MLV-vaccinated beef cattle when revaccinated with an MLV vaccine compared to an inactivated vaccine prior to breeding.

Some work has shown that inactivated vaccines do a good job of boostering intranasal MLV vaccines.  I still believe that a good vaccine program begins with MLV, but inactivated vaccines should become a commonly used tool in our vaccine toolbox.  After all, it’s not your grandpa’s inactivated vaccine anymore; today’s inactivated vaccines offer better flexibility and duration and their advantages should be put to use.