Select Agents and Toxins Exclusions:
Attenuated strains of USDA-only select agents excluded from the requirements of 9 CFR Part 121

African swine fever virus, ASFV-G-Δ9GL/ΔUK (effective January 27, 2020)
The ASFV-G-Δ9GL/ΔUK virus strain is an African swine fever virus (AFSV) double deletion mutant derived from AFSV Georgia strain. Attenuation is provided by the deliberate deletion of both the 9GL and UK genes from the ASFV Georgia strain. The double deletion mutant virus attenuation prevented the development of clinical signs in host animals inoculated with increasing doses of the attenuated live virus and does not pose a severe threat to animal health or animal products.

Reference(s):

1. Arias M, de la Torre A, Dixon L, Gallardo C, Jori F, Laddomada A. Martins C, Parkhouse RM, Revilla Y, Rodriguez F, Sanchez-Vizcaino JM. Approaches and perspectives for development of African swine fever virus vaccines. Vaccines (Basel). 2017 Oct 7;5(4):35. doi:10.3390/vaccines5040035.
2. Galindo I, Alonso C. African swine fever virus: a review. 2017 May10;9(5):103. doi:10.3390/v9050103.
3. Gallardo C, Fernandez-Pinero J, Arias M. African swine fever (ASF) diagnosis, an essential tool in the epidemiological investigation. Virus Res. 2019 Oct2;271: doi:10.1016/j.virusres.2019.197676.
4. Lewis T, Zsak L, Burrage TG, Lu Z, Kutish GF, Neilan JG, Rock DL. An African swine fever virus ERV1-ALR homologue, 9GL, affects virion maturation and viral growth in macrophages and viral virulence in swine. J Virol. 2000 Feb;74(3):1275-1285. doi:10.1128/jvi.74.3.1275-1285.2000.
5. Neilan JG, Zsak L, Lu Z, Burrage TG, Kutish GF, Rock DL. Neutralizing antibodies to African swine fever virus proteins p30, p54, and p72 are not sufficient for antibody-mediated protection.  2004 Feb 20;319(2):337-342. doi:10.1016/j.virol.2003.11.011.
6. O’Donnell V, Risatti GR, Holinka LG, Krug PW, Carlson J, Velazquez-Salinas L, Azzinaro PA, Gladue DP, Borca MV. Simultaneous deletion of the 9GL and UK genes from the African swine fever virus Georgia 2007 isolate offers increased safety and protection against homologous challenge. J Virol. 2016 Dec 16;91(1):e01760-16. doi: 10.1128/JVI.01760-16. Print 2017 Jan 1.
7. Sánchez-Vizcaino JM, Martínez-López, B, Martínez-Avilés M, Martins C, Boinas F, Vial L, Jori F, Marcel E, Etter C, Albina E, Roger FL. Scientific review on African Swine Fever. Scientific Report: European Food Safety Authority; 2009. (CFP/EFSA/AHAW/2007/2).
8. World Organisation for Animal Health (OIE). African swine fever (infection with African swine fever virus) Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2019.
9. Zsak L, Caler E, Lu Z, Kutish GF, Neilan JG, Rock DL. A nonessential African swine fever virus gene UK is a significant virulence determinant in domestic swine. J Virol. 1998 Feb;72(2):1028- 1035. doi: 10.1128/JVI.72.2.1028-1035.1998.

African swine fever virus, ASFV-G-ΔI177LΔLVR (effective March 11, 2021)
The ASFV-G-ΔI177LΔLVR virus strain is an African swine fever virus (AFSV) deletion mutant derived from AFSV Georgia strain. Attenuation is provided by the deliberate deletion of the I177L gene and the Left Variable Region (LVR) which fully deletes the following 9 genes: MGF360-6L, X69R, MGF300-1L, MGF300-2R, MGF300-4L, MGF360-8L, MGF360-9L and MGF360-10L. The genomic modification also causes deletion of the N-terminal portion of the MGF360-4L gene, and the C-terminus portion of the MGF360-11L gene. The deletion mutant virus attenuation prevented the development of clinical signs in host animals inoculated with increasing doses of the attenuated live virus and does not pose a severe threat to animal health or animal products.

References:

1. Arias M, de la Torre A, Dixon L, Gallardo C, Jori F, Laddomada A. Martins C, Parkhouse RM, Revilla Y, Rodriguez F, Sanchez-Vizcaino JM. Approaches and perspectives for development of African swine fever virus vaccines. Vaccines (Basel). 2017 Oct 7;5(4):35. doi:10.3390/vaccines5040035.
2. Borca MV, Ramirez-Medina E, Silva E, Vuono E, Rai A, Pruitt S, Holinka LG, Velazquez-Salinas L, Zhu J, Gladue DP. Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain. J Virol. 2020 Mar 17;94(7):e02017-19. doi: 10.1128/JVI.02017-19.
3. Galindo I, Alonso C. African swine fever virus: a review. 2017 May10;9(5):103. doi:10.3390/v9050103.
4. Gallardo C, Fernandez-Pinero J, Arias M. African swine fever (ASF) diagnosis, an essential tool in the epidemiological investigation. Virus Res. 2019 Oct2;271: doi:10.1016/j.virusres.2019.197676.
5. Neilan JG, Zsak L, Lu Z, Burrage TG, Kutish GF, Rock DL. Neutralizing antibodies to African swine fever virus proteins p30, p54, and p72 are not sufficient for antibody-mediated protection. 2004 Feb 20;319(2):337-342. doi:10.1016/j.virol.2003.11.011.
6. Sánchez-Vizcaino JM, Martínez-López, B, Martínez-Avilés M, Martins C, Boinas F, Vial L, Jori F, Marcel E, Etter C, Albina E, Roger FL. Scientific review on African Swine Fever. Scientific Report: European Food Safety Authority; 2009. (CFP/EFSA/AHAW/2007/2).
7. World Organisation for Animal Health (OIE). African swine fever (infection with African swine fever virus) Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2019.

Avian influenza virus (low pathogenic)
Any low pathogenic strains of avian influenza virus, provided that the individual or entity can identify the agent is within the exclusion category. The Guidelines for Avian Influenza Viruses specify exclusion criteria.

Avian influenza virus (highly pathogenic), recombinant vaccine reference strains of the H5N1 and H5N3 subtypes (effective 5-7-2004)
Several recombinant reference vaccine strains of highly pathogenic subtypes have been excluded based on results from in-vitro and in-vivo studies indicating that these strains were not pathogenic in avian species. The data requirements necessary for exclusion consideration under 9 CFR 121.3(g) [PDF – 243 KB]. Specific reference vaccine strains have not been listed here for proprietary reasons.

Foot-and-mouth disease, FMD-LL3B3D A24 Cruzeiro, vaccine virus (effective April 30, 2018)
The FMD-LL3B3D A24 Cruzeiro vaccine virus is a foot-and-mouth disease (FMD) virus attenuated through the deliberate deletion of a leader sequence of the FMD virus genome. The vaccine virus attenuation prevents replication in target hosts and includes a negative marker in the viral genome to enable differentiation of animals infected versus vaccinated.

Reference(s):

1. Belsham G. Influence of the Leader protein coding region of foot-and-mouth disease virus on virus replication.J Gen Virol. 2013 Jul; 94(7):1486-95
2. Guan S, Belsham G. Separation of foot-and-mouth disease virus leader protein activities; identification of mutants that retain efficient self-processing activity but poorly induce eIF4G cleavage. J Gen Virol. 2017 Apr; 98(4):671-680.
3. Uddowla S, Hollister J, Pacheco JM, Rodriquez LL, Rieder E. A safe foot-and-mouth disease vaccine platform with two negative markers for differentiating infected from vaccinated animals. J Virol. 2012 Nov; 86(21):11675-85.