[Federal Register Volume 87, Number 169 (Thursday, September 1, 2022)]
[Rules and Regulations]
[Pages 53679-53680]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-18973]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 73


Select Agent: Determination That Vaccine Strain, TC-83(A3G) of 
Venezuelan Equine Encephalitis Virus (VEEV) Is a Regulated Strain of 
VEEV

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Regulatory determination.

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SUMMARY: The Centers for Disease Control and Prevention (CDC), located 
within the Department of Health and Human Services (HHS), has 
determined that a modification to the attenuated, excluded strain 
Venezuelan Equine Encephalitis Virus (VEEV) TC-83 has been shown to 
increase its virulence. The modified VEEV strain TC-83(A3G) 
demonstrated increased pathogenicity and lethality. Therefore, the 
modified VEEV strain TC-83(A3G) is not an excluded strain but is a 
select agent and is subject to regulation.

DATES: This action is effective September 1, 2022.

FOR FURTHER INFORMATION CONTACT: Samuel S. Edwin Ph.D., Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Road NE, Mailstop H21-4, Atlanta, Georgia 
30329, Telephone: (404) 718-2000.

SUPPLEMENTARY INFORMATION: VEEV is a member of the genus Alphavirus in 
the family Togaviridae, and is a small, enveloped virus with a genome 
consisting of a single strand of positive-sense RNA. VEEV is a 
mosquito-borne virus that causes encephalitis or encephalomyelitis in 
all equine species and humans.
    The select agent regulations (42 CFR part 73) established a process 
by which

[[Page 53680]]

an attenuated strain of a select biological agent or toxin that does 
not pose a severe threat to public health and safety may be excluded 
from the requirements of the select agent regulations. On February 7, 
2003, VEEV strain TC-83 was excluded from select agent regulations 
because mice vaccinated subcutaneously with the VEEV strain TC-83 
rapidly developed immunity to subcutaneous or airborne challenge with 
virulent VEEV (https://www.selectagents.gov/sat/exclusions/overlap.htm). As such, CDC determined that the attenuated strain did 
not have the potential to pose a severe threat to public health and 
safety.
    As set forth under 42 CFR 73.4(e)(2), if an excluded attenuated 
strain is subjected to any manipulation that restores or enhances its 
virulence, the resulting select agent will be subject to the 
requirements of the regulations. Based on review by subject matter 
experts, CDC has determined that a modification to the excluded 
attenuated VEEV vaccine strain TC-83 has been shown to increase its 
virulence and pathogenicity. An adenine (A) at position 3 in TC-83 has 
been shown to contribute to the attenuation of VEEV. In TC-83(A3G), the 
A has been changed to a guanine (G), which is found in all wild-type 
isolates of VEEV. The reversion of this nucleotide mutation to the 
wildtype nucleotide resulted in increased lethality in mice when 
compared to mice inoculated with the vaccine strain TC-83. Additional 
data determined that the pathogenic effects of TC-83(A3G) are more 
pronounced in young mice. As such, the modification of the excluded, 
attenuated VEEV vaccine strain TC-83 to create VEEV strain TC-83(A3G) 
restores the virus's virulence and therefore, VEEV strain TC-83(A3G) is 
subject to 42 CFR part 73.

Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2022-18973 Filed 8-30-22; 4:15 pm]
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