Why does rabies vaccine cause sarcoma in cats but not human?

What Is Feline Injection-Site Sarcoma (FISS)

• First reported in the scientific literature in 1991 on cats originating from the US states of Pennsylvania, New Jersey and Maryland (1) but actually observed since at least 1987, feline injection-site sarcoma (FISS, Vaccine-associated sarcoma - Wikipedia) isn't unique to inactivated rabies vaccine (2) but can also develop following FeLV (Feline leukemia virus - Wikipedia) vaccine (3), aluminum-adjuvanted vaccines (1), vaccines against feline panleukopenia virus (FPV), feline herpes virus-1 (FHV-1), feline calcivirus (FCV) or even just injections themselves in the absence of vaccines (4).
• Multiple studies found no relationship between vaccine type, brand, nature (modified-live or inactivated) and FISS risk (5, 6, 7).
• Injection-site sarcomas in cat occur even in the absence of vaccines (3, 8), for example following injections of glucocorticoids, antibiotics, anti-flea and painkillers (4).
• Incidence of FISS ranged from 1.3 per 1000 (0.13%) in Canada from 1982 to 1993 (9) to 1 per 10000 (0.01%) in Canada and USA from 1998 to 2000 (10). In other words, relatively low with further reduction in recent years, perhaps as awareness of injection-related risk spread within the veterinary community and efforts were made to identify and mitigate risks.

FISS (Feline Injection-Site Sarcoma) Risk Factors

So what could trigger FISS?

• Risk factors documented thus far include number of injections given in one site (more injections, higher the risk), route (interscapular, scruff of the neck, more risky) and temperature (cold more risky compared to room temperature) (5, see below from 11).
• Adjuvanted vaccines may be more risky since histology and ultrastructural studies of FISS have shown adjuvants like aluminum concentrated within them (12, 13).
• One risk factor may be genetic since risk is higher in siblings of cats with FISS (4). However, as of 2016 FISS genetic risk factors remain as yet undetermined (see below from 14),

'Dr. Boston: Most affected cats are not purebreds; they’re domestic shorthairs from the pound. They’re spayed and neutered. No one knows where their littermates are. It’s difficult to show a genetic predisposition, but we presume it’s there. Some studies show that these cats are predisposed genetically for one of the cancer-promoter genes'

• Research on linking FISS to tumor suppressor p53 - Wikipedia have so far been contradictory and hence inconclusive (15, 16, 17). This might have been due to different studies examining genetically disparate cat populations.

How To Minimize FISS Risk

Finally injection recommendations to minimize FISS occurrence include

• Choosing non-adjuvanted, modified-live or recombinant vaccines over adjuvanted or killed vaccines (18).
• Injecting only at recommended sites, hindlimbs, right forelimb and stringently avoiding interscapular (scruff of the neck) (see below from 11, 18).

Bibliography

1. Hendrick, Mattie J., et al. "Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum." Cancer Research 52.19 (1992): 5391-5394. http://cancerres.aacrjournals.or...

2. Hendrick, M. J., and J. J. Brooks. "Postvaccinal sarcomas in the cat: histology and immunohistochemistry." Veterinary Pathology 31 (1994): 126-126. https://www.researchgate.net/pro...

3. Kass, Philip H., et al. "Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats." Journal of the American Veterinary Medical Association 203.3 (1993): 396-405.

4. Hartmann, Katrin, et al. "Feline injection-site sarcoma ABCD guidelines on prevention and management." Journal of feline medicine and surgery 17.7 (2015): 606-613. https://www.researchgate.net/pro...

5. Kass, Philip H., et al. "Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats." Journal of the American Veterinary Medical Association 223.9 (2003): 1283-1292. https://www.researchgate.net/pro...

6. Wilcock, Brian, Anne Wilcock, and Katherine Bottoms. "Feline postvaccinal sarcoma: 20 years later." The Canadian Veterinary Journal 53.4 (2012): 430. https://www.researchgate.net/pro...

7. Srivastav, Anup, et al. "Comparative vaccine-specific and other injectable-specific risks of injection-site sarcomas in cats." Journal of the American Veterinary Medical Association 241.5 (2012): 595-602. https://www.researchgate.net/pro...

8. Martano, Marina, Emanuela Morello, and Paolo Buracco. "Feline injection-site sarcoma: past, present and future perspectives." The Veterinary Journal 188.2 (2011): 136-141. http://www.ad-domus.it/app/downl...

9. Lester, Sally, Terri Clemett, and Alf Burt. "Vaccine site-associated sarcomas in cats: clinical experience and a laboratory review (1982-1993)." Journal of the American Animal Hospital Association 32.2 (1995): 91-95.

10. Gobar, Glenna M., and Philip H. Kass. "World wide web-based survey of vaccination practices, postvaccinal reactions, and vaccine site-associated sarcomas in cats." Journal of the American Veterinary Medical Association 220.10 (2002): 1477-1482. http://citeseerx.ist.psu.edu/vie...

11. Ladlow, Jane. "Injection Site-Associated Sarcoma in the Cat Treatment recommendations and results to date." Journal of feline medicine and surgery 15.5 (2013): 409-418. http://felineasthma.org/vas/vasc...

12. Hendrick, M. J., et al. "Comparison of fibrosarcomas that developed at vaccination sites and at nonvaccination sites in cats: 239 cases (1991-1992)." Journal of the American Veterinary Medical Association 205.10 (1994): 1425-1429.

13. Madewell, B. R., et al. "Feline vaccine-associated fibrosarcoma: an ultrastructural study of 20 tumors (1996–1999)." Veterinary Pathology Online 38.2 (2001): 196-202. An Ultrastructural Study of 20 Tumors (1996-1999)

14. Boston, Sarah. "The Feline Sarcoma Controversy: Where Do We Stand?." http://www.cliniciansbrief.com/s...

15. Banerji, Nilanjana, and Sagarika Kanjilal. "Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma." American journal of veterinary research 67.10 (2006): 1766-1772.

16. Banerji, Nilanjana, Vivek Kapur, and Sagarika Kanjilal. "Association of germ-line polymorphisms in the feline p53 gene with genetic predisposition to vaccine-associated feline sarcoma." Journal of Heredity 98.5 (2007): 421-427. Association of Germ-line Polymorphisms in the Feline p53 Gene with Genetic Predisposition to Vaccine-Associated Feline Sarcoma

17. Mucha, D., et al. "Lack of association between p53 SNP and FISS in a cat population from Germany." Veterinary and comparative oncology 12.2 (2014): 130-137.

18. Scherk, Margie A., et al. "2013 AAFP feline vaccination advisory panel report." Journal of feline medicine and surgery 15.9 (2013): 785-808. https://www.researchgate.net/pro...

Thanks for the R2A, Huang ZheYu.