FIV Vaccine Brief

The prevalence of feline immunodeficiency virus infection in the feral cat population is similar to that in the general cat population.

Since March, when the Department of Agriculture licensed the first commercial vaccine for feline immunodeficiency virus, the American Association of Feline Practitioners and the Cornell Feline Health Center have been fielding a flood of questions about the vaccine.

So much so that the AAFP decided it would be worthwhile to develop a resource that addresses the fundamental questions that have arisen.

Various AAFP panels on vaccines and retroviruses were involved in the extensive development process. Outside input was sought from certain experts and the vaccine manufacturer.

Dr. James Richards is director of the Cornell Feline Health Center, and a board member of the AAFP and co-chair of several of its feline guidelines panels. "The big question we've been receiving has been on testing"—an area he said neither the vaccine label nor the initial advertising material addresses. "Veterinarians just did not realize that cats that were vaccinated would test positive for antibody. Many of those who did understand that cats would test positive on the in-house kits failed to realize that they would also test positive on western blot."

As veterinarians become more educated consumers, he added, they are seeking independent information when new vaccines are released.

IDEXX Laboratories, the manufacturer of the FIV diagnostic test, said it is evaluating methods that would allow differentiation of vaccinated cats from infected cats when necessary. Meanwhile, the manufacturer sponsored several teleconferences in which Dr. Richards discussed FIV infection, diagnosis, and vaccination. Staff from a thousand veterinary hospitals reportedly listened in to the ones in August.

At the Sept. 19 teleconference, which stretched to two hours to accommodate audience questions, some important points about testing and vaccination were clarified.

There is undertesting for FIV in cats that are taken to a clinic with vague signs of illness, Dr. Richards said. He also encourages veterinarians to test cats that a client intends to adopt—whether found homeless or at a shelter or pet shop. This is true regardless of whether the household has other cats.

Periodic testing is indicated for cats that initially test negative but live with an FIV-infected cat or with cats of unknown infection status, and those that are allowed unsupervised outdoor activity.

Postexposure testing of a cat that has been bitten is also justified, Dr. Richards said. Most cats that become infected will test positive within 60 days postexposure, usually in two to six weeks.

One reason the AAFP decided to revisit its retrovirus testing guidelines was to emphasize the importance of testing kittens.

"A misimpression was given in the first set of guidelines that you cannot test kittens because the tests are meaningless in kittens less than six months of age," Dr. Richards noted. "That was an erroneous conclusion, one that required some clarification."

Most kittens will test negative, indicating they're uninfected. But the confusion is because kittens can test positive on the antibody test if an infected queen passes on antibody to them.

Even if they test positive, infection is unlikely, Dr. Richards said. Test every 60 days up to six months, he said. If they become seronegative, it's likely the kittens are not infected.

A caller asked whether it's possible and useful to test for FIV subtype. A laboratory could sequence the isolates, Dr. Richards replied, but it would be of no practical value. There is no compelling evidence of a correlation between subtype and severity of illness.

So far, five subtypes or clades of FIV have been identified—A, B, C, D, and E. Worldwide, 80 percent of the subtypes are A and B. In this country, A and B predominate. Subtype D is common in Asia.

Most of the cats that have tested positive in the United States have subtype B virus, and most have been in the East. In the West, subtype A is seen most often. The question then arises, can FIV tests detect all the field strains?

Dr. Richards said antibody-based tests should detect infection, irrespective of the FIV subtype, but he is concerned about a high number of false-negative test results when using polymerase chain reaction-based assays. A recent study showed a PCR-based assay was false-negative on one of 10 tests for subtype A and one of 12 for subtype B. In general, he considers the PCR assay a wonderful tool, but he is concerned about its current usability as a commercial diagnostic test for FIV.

Asked about the potential for developing an antigen test, Dr. Richards said that, unlike feline leukemia virus-infected cats, FIV-positive cats are not highly antigenemic, so he doesn't foresee one.

The discussion then shifted from testing to vaccination. The inactivated, killed FIV vaccine contains isolates of two subtypes or clades—A and D.

It's important to note that cats can be both vaccinated and infected, Dr. Richards noted. They could have been infected prior to vaccination or despite vaccination. For that reason, many people have asked whether antibody tests are worthless.

"I'd be quick to point out that, despite the difficulties that we have with positive test results in vaccinated cats and interpreting those, negative test results still remain very meaningful to us," Dr. Richards said, "and at this point, most cats are going to test negative."

A caller who works with rescue groups asked what advice to give them. Dr. Richards suggested advising them it may not be cost effective to routinely test the feral cat population, since the prevalence of FIV infection there is similar to that of the general cat population.

The efficacy of the FIV vaccine has raised many questions. For the laboratory study of efficacy required by the Department of Agriculture, the FIV manufacturer vaccinated 25 specific pathogen-free kittens. Approximately a year following vaccination, the vaccinated kittens and a control group of 19 (initially 20) kittens were challenged intramuscularly with subtype A virus. "The efficacy figure, when we look at something called the preventable fraction, was around 82 percent, so there was quite a difference between the vaccinated cats and nonvaccinated cats," Dr. Richards said.

Given that the cats in the efficacy study were challenged with subtype A, however, no information is available about protection from subtype B. A frequent concern is whether the vaccine is then less effective on the East Coast, where subtype B appears more prevalent. Although no data were available, Dr. Richards noted this is a big concern about HIV and FIV vaccines, because the diversity of the viruses demands broad protection against field isolates.

Addressing veterinarians, Dr. Richards said, "The question then comes up: do I use the vaccine or not use the vaccine? In my view, the major concern is testing confusion. When clients come to you with questions about using the vaccine, it's a situation where you need to spend some time talking about the pros and cons of vaccination.

"If the client decides, under your counsel, that vaccination is something they want to do, I would certainly make sure to test that cat beforehand."

Susan C. Kahler

American Association ol Feline Practitioners Information Brief:

In response to inquiries regarding Fel-O-Vax® FFV
September 2002
Fel-0-Vax® FIV is an inactivated, dual subtype (based on strains of Petaluma subtype A and Shizuoka subtype D) feline immunodeficiency virus (FIV) vaccine. The adjuvanted whole virus vaccine was released in July 2002, and is produced by Fort Dodge Animal Health.

Testing implications

•Cats vaccinated with Fel-0-Vax® FIV develop antibodies to the inactivated virus present in the vaccine.
•Currently available antibody-based FIV diagnostic tests (e.g.,SNAP® Feline Combo, PetChek® FIV Ab plates,and Western blot) available in the United States and Europe cannot distinguish cats vaccinated with Pel-P-Vax® FIV from FIV-infected cats or from cats that are both vaccinated and infected.
•Negative FIV-antibody test results remain reliable (see the 2001 Report of the AAFP/AFM Advisory Panel on Feline Retrovims Testing and Management at http://www.aafponline.org/about/guidelines.htm). But until tests that differentiate vaccinated cats from infected cats become readily available, it will be impossible to assess the significance of positive test results. (Is a positive-testing cat infected, vaccinated, or both?) Some consequences of this ambiguity:
•The benefit of testing and isolating FIV-infected cats—the mainstay of reducing viral transmission—will be diminished if vaccinated cats are erroneously assumed to be non-infectious.
• It will be impossible to ascertain the safety of adopting positive-testing cats into households with uninfected cats.Vaccinating all the residents prior to adoption may provide some protection, but it is unrealistic to expect all vaccinates to be protected.
• Because infected cats—either healthy or ill—will be difficult to identify, the delivery of the specialized care they require will be significantly compromised.
• Kittens born to vaccinated queens will likely test positive for passively acquired FIV antibody According to studies conducted by the manufacturer, antibody levels drop to levels that won't interfere with test results by the time kittens reach 8 weeks-of-age.
•Some shelters and other facilities designed to house strays often euthanize cats with positive FIV test results, so previously vaccinated uninfected cats may needlessly undergo euthanasia. Permanently identifying cats vaccinated with Fel-0-Vax® FIV (e.g., using a microchip or tattoo) has been suggested as a means of identifying vaccinated cats, thus sparing them from euthanasia. Yet previous vaccination does not rule out infection nor prevent the subsequent placement of infected cats.

Alternate test methods

Virus isolation (VI) has been suggested as another means of confirming or ruling out FIV infection, but VI has
a multitude of limitations that make it impractical as a routine diagnostic tool in private practice settings.
Polymerase chain reaction (PCR)-based tests can potentially differentiate infected cats from vaccinates by
identifying proviral DNA present in blood cells. Most, if not all, PCR-based assays available at the time of this writing
present the following difficulties:

• Information regarding the sensitivity, specificity, and validation is largely lacking.
•Test reagents have not been standardized.
•Ability to detect various field strains to which cats might be exposed has been inadequately explored.
•Quality control within laboratories performing PCR-based FIV tests must be stringent if accurate results are to be obtained,yet mandatory quality control standards to which diagnostic laboratories must adhere are lacking.

PCR-based tests will become increasingly available to veterinarians, and it will be difficult to assess the reliability of test results until the shortcomings noted above are addressed. Refinements of PCR-based systems may resolve some of these issues. However, at the time of this writing, a validated PCR test that will reliably identify all infected cats or that will distinguish infected cats from those vaccinated with Fel-O-Vax® FIV is not available to clinical practitioners. It should be noted that PCR test methodology cannot be modified for in-clinic use, and it is unlikely that a point-of-care test will be available in the foreseeable future.
Vaccine efficacy
FIV is commonly classified into five different subtypes (A, B, C, D, and E) based upon genetic variation within one section of the virus envelope gene. Subtypes A and B are the predominant subtypes in the United States. Substantial genetic variation exists both within and between the various subtypes (also called genotypes or clades). Experimental FIV vaccines reported thus far in the literature have demonstrated poor cross protection between subtypes (e.g., vaccines based on subtype A virus have shown decreased protection against subtype B challenge).
As a condition of licensure,the United States Department of Agriculture (USDA) requires manufacturers to determine vaccine efficacy based upon results of laboratory studies. Accordingly, 45 eight week-old specific pathogen free kittens were randomized into two groups: 25 were vaccinated with Fel-O-Vax® FIV three times three weeks apart while 20 kittens served as non-vaccinated controls. Approximately one year later, both groups were challenged intramuscularly with a subtype A virus that differed by 10% in a portion of the envelope gene from the subtype A virus used in the vaccine. The preventable fraction (defined as the proportion of cats protected by vaccination in excess of the proportion that is naturally resistant) was calculated to be 0.82 (82%).
Challenge models that accurately reflect "real world" exposures to infectious agents are difficult to design and control, expensive, and involve large numbers of cats. In addition, they often require several years of data collection to obtain meaningful results. Laboratory challenges of the kind required by the USDA provide necessary and valuable information, but for reasons of practicality and expense, they may not reflect vaccine performance in the field. Although these efficacy figures are encouraging, it is possible that fewer than 82% of vaccinated cats will be protected from the vast array of FIV genetic variants to which they may be exposed in nature. Therefore, while reasonable to expect that some cats vaccinated with Fel-O-Vax® FIV will be protected from infection, others certainly will not.

Conclusion

The absence of tests that distinguish cats vaccinated with Fel-O-Vax® FIV from infected cats, coupled with questions regarding the vaccine's ability to induce protection against all the subtypes and strains of FIV to which cats might be exposed, makes the decision to recommend use of this product far from straightforward. It is crucial that clients are adequately informed about the vaccine's impact on future test results, and their decision should be reached only after careful consideration of both positive and negative implications. If the decision ultimately falls in favor of vaccination, cats should test negative immediately prior to receiving Fel-O-Vax8 FIV

This document has not undergone peer review by the AVMA.
Opinions expressed are not necessarily those of the
American Veterinary Medical Association.
JAVMA, Vol 221, No. 9, November 1, 2002