The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity

Abstract

Background: Western Equine Encephalitis (WEE) is a naturally acquired infection and potentially devastating bioweapon, with no specific human countermeasures. An experimental inactivated Western Equine Encephalitis Vaccine (WEEV; WEE TSI-GSD 210) has been used under an IND (investigational New Drug) protocol at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976.

Methods: Over 24 years from 1987 to 2011, 876 subjects received 3 primary vaccine doses under 3 studies with 1,537 booster doses administered (FY87-8, phase 2, laboratory workers, vaccine lots 1-81-1, 1-81-2, and 2-1-91; FY99-12, phase 2 laboratory workers, lot 2-1-91; and FY09-02, phase 1 healthy volunteer, lot 3-1-92). Post-vaccination safety and immunogenicity [plaque reduction neutralization test 80% (PRNT₈₀) > 1:40] were analyzed.

Results: Overall PRNT₈₀ response to the primary series in FY87-8 was 42% (326/770) but dropped to 16% (14/87) in FY99-12, prompting study FY09-02, which achieved 89% (17/19). The first booster response rate was 68% (814/1194) in FY87-8, 53% (171/324) in FY99-12, and 100% (10/10) in FY09-02. The majority of definitely related adverse reactions (AEs) were mild and local with no definitely related serious AEs. No laboratory acquired WEE infection was documented during this period despite 4 reported exposures in vaccinated subjects.

Conclusion: The TSI-GSD 210 WEE vaccine was immunogenic, safe and well tolerated. Use of this vaccine could be considered in an emergency setting. Despite decades of safe and effective use under IND, full licensure is not planned due to manufacturing constraints, and a strategic decision to develop alternatives.

Clinical trial registration: https://clinicaltrials.gov/, identifier NCT01159561.

Keywords: Western Equine Encephalitis; clinical trial; immunogenicity; inactivated; vaccine.

Figure 1

CONSORT diagram of study enrollment. ^*Rollovers (subjects recruited from previous protocols); ^**No more than two boosters required within this protocol; ^***Relocation (subjects moved due to new job).

Figure 2

In FY87-08 protocol, post primary^* GMT (Geometric Mean Titers) was 23.3 [21.5, 25.2], and post booster^* GMT was 72.2 [63.3, 82.4]. In FY99-12, post primary^† GMT (Geometric Mean Titers) was 14.1 [12.1, 16.5], and post booster^† GMT was 36.9 [30.1, 45.3]. In the FY09-02 protocol, GMT day 56^‡ was 98.1 [58.6, 164.3], day 180^‡ (pre-6 month boost) was 25.8 [9.7, 68.9], day 210^‡ (post 6-month boost) was 557.2 [376.8, 823.8], and day 360 was 121.3 [62.1, 236.8]. Thus, prior to the 6-month boost, the average titer was <1:40, justifying the need for the 6-month boost. ^*Titers collected 14–56 days post vaccination. ^†Titers collected 23–42 days post-vaccination. ^‡Titers collected 21–35 days post-vaccination.

Figure 3

Post-Primary series PRNT₈₀ immune response to WEE vaccine by year within FY87-8 and FY99-12 (1987–2005). The immunogenicity of WEE TSI-GSD 210 appeared to decline from 53 to 23%.

Figure 4

Post-boosters PRNT₈₀ immune response to WEE vaccine by year within FY87-8 and FY99-12 (1987–2006). Immunogenicity of WEE TSI-GSD 210 appeared to decline from 77–58%.