Feline viral respiratory disease: To vaccinate or not to vaccinate? (Proceedings)

Feline Viral Respiratory Disease: Etiology, Clinical Signs and the Carrier State

Feline herpesvirus-1 (FHV1) and feline calicivirus (FCV) are the two major viral causes of upper respiratory tract disease (URD) in cats.

Feline herpesvirus 1 is a large, enveloped, DNA virus that causes feline viral rhinotracheitis, a disease with signs that include sneezing, ocular and nasal discharges, conjunctivitis, and pneumonia. It has also been associated with oral ulceration, keratitis, corneal ulceration, eosinophilic dermatitis and stomatitis, and abortion in pregnant cats. Severe generalized disease, with necrotic hepatitis, and CNS signs, may also occur. After infection, the virus almost always establishes latency in the neural tissues of the head, especially the trigeminal ganglia, and reactivation may occur following stress, with viral shedding with or without clinical signs of disease. The first strain of FHV1 was isolated from kittens with URD in 1958 (C27). Since then, many strains of varying virulence have been isolated worldwide, which cannot be differentiated antigenically. Although genotypic differences between strains have been demonstrated (Hamano et al, 2005), more work is required to determine whether these correlate with virulence. In the mid 1970s, an attenuated strain, F2, was evaluated for its ability to protect cats against intranasal challenge, and was found to dramatically reduce the severity of signs in cats challenged shortly after vaccination (Bittle and Rubic, 1975). Most of the early studies challenged cats a few weeks after the booster vaccination.

FCV is a nonenveloped RNA virus that is relatively resistant in the environment, surviving days to several weeks at room temperature. There are over 100 different FCV strains that cross-react serologically. The degree of cross-reaction is sufficient to classify them into a single serotype. A marked level of strain diversity exists in large cat populations, such as those found in shelters, and cats can be simultaneously infected by several different strains. Typically, infection is manifested by fever, conjunctivitis, rhinitis, oral ulcerations and/or chronic stomatitis, although occasionally skin ulcerations, lameness and pneumonia may occur. Following infection, a small percentage of cats become chronic carriers, with virus being shed from the oropharynx for months to years in the absence of clinical signs; this virus can mutate slowly over time, allowing it to evade the host immune response. More recently, FCV has been rarely associated with a severe systemic disease (virulent systemic disease, VSD) characterized by subcutaneous edema, and ulceration of the mouth and skin, especially on the pinnae and pawpads and nares. Other lesions include pneumonia, pancreatitis, and necrosis of the liver and spleen. Adult, vaccinated cats have been most severely affected, and in each outbreak, the strain of FCV appears to differ, although all VSD strains infect tissue culture more efficiently than non-VSD strains (Ossiboff et al, 2007). Outbreaks have occurred in the US and the UK. Most have followed introduction of cats from shelters into another population, and all have been self limiting. A vaccine for FCV was first introduced shortly after that for FVR, and the two were combined and evaluated as both intranasal and parenteral vaccines in 1976 and 1977 (Scott, 1977). The FCV vaccine has always contained the F9 or 255 strains of FCV.

How effective are feline respiratory viral vaccines?

Based on the results of challenge studies, feline viral respiratory vaccines are generally effective against reducing respiratory disease, but do not protect against infection or development of the carrier state. This is reflected by the fact that the prevalence of FCV and FHV1 has not changed considerably in the cat population since the introduction of these vaccines. Factors that may affect whether an individual cat contracts respiratory disease after vaccination may depend on factors such as the virus strain, the challenge dose, environmental temperature and humidity, and the presence of underlying immunosuppressive disease or other concurrent disease.

Vaccination for FHV1 has been shown to reduce shedding following challenge, but some FCV vaccines have been associated with increased shedding after challenge.

The effect of vaccination on latency and reactivation for FHV1 requires further study. There is some evidence that vaccinated cats may shed less virus following reactivation. Whether vaccination reduces the chance of reactivation of FHV1 is not known. Intranasal vaccines can become latent, but whether this is the case for parenteral vaccines is not clear.

Scott and Geissinger (1999) reported persistent antibody titers against FHV1 and FCV for > 3 years after vaccination with an inactivated vaccine and partial protection from challenge > 7 years after vaccination, with reduction of signs by about 50% for FHV1 and 63% for FCV. Titers gradually declined over the 7 years of the study, but challenge was followed by a rapid anamnestic response. Based on the results of historical control studies using the same vaccine, it appears possible that the degree of protection may wane over time in cats that do not receive natural boostering, especially for FHV1. More recently, significant protection from clinical signs was demonstrated following challenge with FHV1 and FCV 3 years after vaccination with a modified live viral vaccine, although the degree of protection was greater for FCV than FHV1 (Gore et al, 2006).

Because of concerns that the F9 FCV strain might not provide adequate protection against currently circulating strains of FCV, that may have partly emerged as a result of immune pressure, an inactivated, nonadjuvanted bivalent vaccine containing two FCV strains has recently been marketed in Europe (Poulet et al, 2005). A recent study from the UK however showed that the F9 strain still generated cross-reactive antibody to a large number of currently circulating strains (Porter et al, 2007).

Traditional FCV vaccines do not appear to protect cats against VSD. As a result, a VSD vaccine was introduced in 2007. This is an inactivated, adjuvanted vaccine containing a single VSD strain. Because VSD is an uncommon disease, has involved varying strains of FCV, and is unlikely to spread widely in the cat population, the potential risks of vaccination with an inactivated, adjuvanted vaccine must be carefully weighed with the likely benefit for this disease.

Recent evidence has shown that intranasal vaccination may also provide more rapid protection in the face of an outbreak or introduction to contaminated premises, and only a single dose is required; they are also less likely to be associated with VSA

The amount of maternal antibody a kitten is born with varies from cat to cat, depending on the antibody titer of the queen and the amount of colostrum. Finally, there has been mounting evidence that some cats may retain enough maternal antibody to resist vaccination at 12 weeks of age (Dawson, 2001; Poulet, 2007). Because of this, the updated AAFP feline vaccination guidelines have recommended that kittens receive their last booster no earlier than 16 weeks of age.

How safe are feline respiratory viral vaccines?

Adverse effects of feline respiratory viral vaccines that have been considered include:

1. Postvaccinal sarcomas. Although rare, postvaccinal sarcomas have been reported at the site of previous FVRCP vaccination.

2. Postvaccinal respiratory disease. Parenteral vaccination may be followed by postvaccinal respiratory disease if vaccine virus is inhaled or ingested during vaccination. Intranasal vaccines can induce mild to moderate signs of respiratory tract disease shortly after vaccination. Despite this problem, renewed interest in intranasal vaccines has occurred recently because of the lack of association with fibrosarcomas and their ability to protect rapidly.

3. Postvaccinal lameness. This has been uncommonly reported after FCV vaccination, especially of young kittens.

4. Nephritis. Currently, more evidence is required to determine whether vaccination with feline respiratory viral vaccines triggers nephritis in cats. Because vaccine virus is grown in feline kidney cells, concern has been raised that induction of an antibody response against proteins from these cells that contaminate the vaccine may lead to autoantibody formation against kidney tissue. Although antibodies against CRFK cells were documented following parenteral vaccination, renal disease did not occur over the 56 week time period of the study (Lappin et al, 2005). Intranasal vaccination has not been associated with antibody formation. More recently hypersensitization against CRFK cell lysates over a 2 year period was shown to be associated with lymphocytic plasmacytic renal inflammation in 3 of 6 cats (Lappin et al, 2006).

5. Shedding of vaccine virus. Cats inoculated with MLV FCV vaccines can shed virus from the oropharynx, and this virus has the potential to mutate and acquire virulence over time, although currently the significance of this is unknown. The importance of FHV1 vaccine virus in the population is also largely unknown. The introduction of 'marker' vaccines, such as deletion mutant vaccines, should be encouraged such that vaccine virus may be differentiated from field virus.

It should be emphasized that decisions regarding vaccination should be tailored to each animal, and vaccination should not be used as a substitute for control measures.

References: Available on request