Immunity and Serum Neutralization Titers for Cattle

Guide B-229
Revised by John C. Wenzel
College of Agricultural, Consumer and Environmental Science, New Mexico State University.


Author: Extension Veterinarian, Department of Extension Animal Sciences and Natural Resources, New Mexico State University. Private Veterinary Practitioner, Albuquerque, New Mexico. (Print friendly PDF)

A herd of white cows with horns stands in a field, with the focus on a cow in the forefront. The cow in the foreground is positioned in a side view, staring directly at the camera. All the cows are tagged with yellow ear tags, and the image captures their full bodies in the open field.

Photo by Josh Bachman. NMSU, 2021.

INTRODUCTION

The immune response of cattle is a very complex system. For the purposes of this guide, we will discuss the immune response in a very general sense. The immune response depends on several factors, including the dam’s immune status, the quantity and quality of colostrum she produces, the level of maternal antibodies the calf receives from colostrum, the calf’s nutritional, vitamin, and mineral status, and its prior exposure to pathogens and vaccination history. These are just some of the factors that influence an immune response.

A couple of definitions will help in understanding the immune response. An antigen is a toxin, protein, or other foreign substance that causes the body to initiate an immune response, usually resulting in the production of antibodies against the foreign substance. Antibodies are proteins produced by the body’s immune system in response to recognition of a foreign substance (antigen), which will help neutralize the effects of that substance.

INNATE AND ACQUIRED IMMUNITY

Innate immunity is the capability an animal is born with to respond to an antigen intrusion. The body is born with a very general response that will neutralize or at least respond to an antigen when introduced. Innate immunity has many components, like physical barriers such as skin, mucus membranes, and stomach acids to name a few; there are frontline responses on the cellular level as well. Innate immune responses are usually very general and do not target specific antigens.

Acquired immunity is a much more specific response. This response occurs at the cellular level and involves many systems, including the lymphatic system, white blood cells, and local cells in the area of exposure. Acquired immunity is being refined, added to and enhanced throughout a lifetime.

ANTIGENS AND ANTIBODIES (HUMORAL RESPONSE)

In order to produce antibodies, the immune system must be exposed to an antigen, which results in the production of a particular antibody. This exposure can be from natural exposure or vaccination. When the body is exposed to an antigen, many processes are engaged to produce antibodies against that antigen. How and where in the body a particular antigen is presented to the immune system can influence the antibody production. These principles are the basis for the types, routes, and frequency of administration of vaccines. We have learned to manipulate the immune response and prepare an animal’s body for the possibility of re-exposure to a particular antigen.

ACQUIRED RESPONSE (CELL MEDIATED IMMUNITY)

This response is much more specific and targeted to a specific antigen. Components of the humoral response may be included in the acquired response but also contains a response at the cellular level. This is very important when developing immunity against viral agents. Certain vaccines, called modified live virus vaccines (MLV’s), can activate the Cell Mediated Immunity (CMI) system whereas killed vaccines cannot unless the animal has been “primed” by using a MLV in the somewhat recent past. To initially activate a CMI response, viral replication must occur in the animal’s body, either by vaccination or by exposure to the viral disease. Once activated, subsequent MLV vaccinations greatly enhance the CMI response, whereas subsequent vaccination with killed vaccines mildly to moderately enhance the CMI response. MLV vaccines should be included in all vaccine programs, especially when vaccinating calves and young cattle.

SERUM NEUTRALIZATION TITERS

There are many tools available to evaluate the immune system. One of these tools is serum neutralization titers (SN titers). An SN titer is a measure of circulating antibodies and the level at which the antibodies no longer neutralize a known amount of antigen added to the test sample. While SN titers are a very rough measure of the immune strains or types that have similar cores but have different aspects that cause different effects on the body. To submit a sample for SN testing, a blood sample is drawn and placed into a tube that will allow the blood to clot. The sample is spun in a centrifuge to separate the serum from the cells, and the serum is used for testing. A measured amount of serum is placed into a test well, and each subsequent test well contains a half dilution of the previous well. This creates a series of dilutions: the first well is a 1:2 dilution, the next is 1:4 dilution, followed by 1:8, 1:16, 1:32, 1:64, and so on. Next, a known amount of antigen for a particular disease is added to each test well. The last well in which this known amount of antigen is neutralized is the SN titer. For example, if the antigen is neutralized at the 1:32 dilution but not at the 1:64 dilution, then this sample has a SN titer of 1:32. We know there was enough circulating antibody present in the 1:32 dilution to neutralize the known amount of antigen that it was challenged with.

The higher the number of dilutions, the greater the amount of circulating antibody. While this does not mean greater immunity to the particular disease, it does suggest that the higher the titer, the better prepared the animal may be to re-exposure to the disease tested for. Also, generally speaking, the immune response to the natural disease cannot be differentiated from the immune response created by vaccination. If an SN titer is negative or zero, then we do not know if exposure to the tested disease has never occurred or took place so long ago that circulating antibodies have decayed and disappeared. If no SN titer is detected, it suggests that this particular animal may be susceptible to the tested disease.

If an animal has a titer of 1:4, we can make some general statements. For example, we know this animal has not been recently exposed to or vaccinated for the tested disease. We know this animal has produced antibodies, so exposure took place at some time. If an animal has a titer of 1:1,024, this suggests more recent exposure or vaccination. In some cases, the titer will be greater than the testing capabilities. At a point, or “end point,” the test will not be carried out any farther. For example, with bovine viral diarrhea (BVD) testing, the end point used by the Colorado State University Diagnostic Laboratory is 16,384. So, a titer greater than this will be reported as >16,384. With some diseases, the titers generated by natural exposure to disease are much greater than what is generated by vaccination. Also, the type of vaccine, such as killed versus modified live vaccines, will influence the amount of circulating antibody present. Generally, modified live vaccines create higher SN titers.

SUMMARY

Understanding these basic principles will help you interpret SN titers. When sample results are obtained, you should already know about vaccine history and frequency. Then the SN titer can be used as a general guideline. It is best used to look at a group of animals rather than an individual. Questions such as “Have these cattle been vaccinated or exposed to a particular disease?” or “Is my vaccination program giving me the duration I am seeking?” can be evaluated using SN titers. It may be prudent to run a few samples on incoming cattle or new additions to look at background immune status. This may help you decide whether or not to vaccinate new additions. While SN titers are not the “end all, be all,” they are a tool that when used and interpreted correctly can be a very valuable diagnostic test, providing information to aid many management decisions.

FOR MORE INFORMATION

For more information on evaluating the immune status of your cowherd, contact your local veterinarian.

For more general information on SN titers or immunity, contact the author at jwenzel@nmsu.edu or (575) 534-7562, or the Department of Extension Animal Sciences and Natural Resources (https://easnr.nmsu.edu/). For other Extension livestock and range publications, visit https://pubs.nmsu.edu/_b/ 

For Further Reading

B-222: Cattle Vaccination and Immunity
https://pubs.nmsu.edu/_b/B222/

B-223: Calf Vaccination Guidelines
https://pubs.nmsu.edu/_b/B223/

B-224: Cow Herd Vaccination Guidelines
https://pubs.nmsu.edu/_b/B224/

B-226: Increasing the Effectiveness of Modified Live Vaccines
https://pubs.nmsu.edu/_b/B226/


Original PublicationJohn C. Wenzel, Extension Veterinarian and Private Veterinary Practitioner. November 2015.


Photo of John C. Wenzel.

John C. Wenzel is the Extension Veterinarian in the Department of Extension Animal Sciences and Natural Resources at NMSU. He earned his B.S. from NMSU and his DVM from Kansas State University College of Veterinary Medicine. His work focuses on cow/calf medicine and preventive health programs for livestock producers in southwestern New Mexico.


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Revised December 2024. Las Cruces, NM.