Safety and immunogenicity of an inactivated eastern equine encephalitis virus vaccine

Benjamin C. Pierson*, Anthony P. Cardile, Arthur C. Okwesili, Isaac L. Downs, Ronald B. Reisler, Ellen F. Boudreau, Mark G. Kortepeter, Craig D. Koca, Manmohan V. Ranadive, Patricia L. Petitt, Niranjan Kanesa-thasan, Robert G. Rivard, Dani L. Liggett, Jeannine M. Haller, Sarah L. Norris, Bret K. Purcell, Phillip R. Pittman, David L. Saunders, Maryam Keshtkar Jahromi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Eastern equine encephalitis virus (EEEV) is a mosquito borne alphavirus spread primarily in Atlantic and Gulf Coast regions of the United States. EEEV is the causative agent of a devastating meningoencephalitis syndrome, with approximately 30% mortality and significant morbidity. There is no licensed human vaccine against EEEV. An inactivated EEEV vaccine has been offered under investigational new drug (IND) protocols at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976. Methods: Healthy at-risk laboratory personnel received inactivated PE-6 strain EEEV (TSI-GSD 104) vaccine under two separate IND protocols. Protocol FY 99–11 (2002–2008) had a primary series consisting of doses on day 0, 7, and 28. Protocol FY 06–31 (2008–2016) utilized a primary series with doses on day 0 and 28, and month 6. Participants with an inadequate immune response, plaque reduction neutralization test with 80% cut-off (PRNT80) titer < 40, received booster vaccination. Volunteers with prior EEEV vaccination were eligible to enroll for booster doses based on annual titer evaluation. Results: The FY06-31 dosing schema resulted in significantly greater post-primary series immune response (PRNT80 ≥ 40) rates (84% vs 54%) and geometric mean titers (184.1 vs 39.4). The FY 06–31 dosing schema also resulted in significantly greater cumulative annual immune response rates from 1 to up to 7 years post vaccination (75% vs 59%) and geometric mean of titers (60.1 vs 43.0). The majority of probably or definitely related adverse events were mild and local; there were no probably or definitely related serious adverse events. Conclusions: Inactivated PE-6 EEEV vaccine is safe and immunogenic in at-risk laboratory personnel. A prolonged primary series, with month 6 dose, significantly improved vaccine immunogenicity both post-primary series and longitudinally on annual titers. Despite decades of safe use under IND, full licensure is not planned due to manufacturing constraints, and ongoing development of alternatives.

Original languageEnglish
Pages (from-to)2780-2790
Number of pages11
Issue number20
StatePublished - 12 May 2021


  • Alphavirus
  • Arbovirus
  • EEE
  • EEEV
  • Eastern equine encephalitis virus
  • Vaccine


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