A Rift Valley Fever Vaccine Trial

Abstract

A formalin-inactivated Rift Valley fever vaccine, originally produced in primary monkey kidney cells, has been used to protect laboratory workers. A trial of a modified vaccine, newly formulated in well-characterized diploid fetal rhesus lung cells, was conducted with 114 men aged 19--24 years. Of the 107 subjects who received up to three injections of 0.1 to 1 ml vaccine (an additional seven received a placebo) one had a local hypersensitivity-type reaction and another a generalized urticarial syndrome. Both cases had a prior history of hypersensitivity states. No pyrogenicity was detected and only insignificant systemic reactions were recorded. Mild and transient local reactions ranged from 5% at the lowest dose level to 43% at the highest. Serologic response, as assessed by plaque reduction neutralizing antibody titers, was dose dependent. Within a single vaccine lot tested at multiple dose levels, peak (day 42) geometric mean titers ranged from 48 (at 0.1 ml x 3) to 436 (at 1.0 ml x 3). Reciprocal titers of greater than or equal to 40 are considered to be protective. Comparison of three lots at the 0.5 ml level indicated between lot variability, though this was not statistically significant. A sharp decline in antibody titers was observed in all vaccination groups by day 84; six months after vaccination apparently protective antibody titers were present only in groups that received 1 ml x 3 and 0.5 ml x 3 of the most antigenic lot of vaccine. These results suggest that 1) the vaccine is generally nonreactogenic, but individuals with a prior history of hypersensitivity states should be observed for allergic side effects; 2) existing vaccine supplies cannot be extended by using lower dose levels without a lower and less sustained serologic response; 3) a booster dose is necessary six months or more following the primary series; 4) although the current TSI-GSD-200 vaccine is immunogenic, a more potent vaccine is needed.

Development of a Novel, Single-Cycle Replicable Rift Valley Fever Vaccine

“…Formalin-inactivated RVFV vaccine requires several immunizations to induce and maintain protective immunity [49], [50]. In contrast, several attenuated RVFV mutants, including MP-12, MP-12-derived mutants carrying a modified cellular gene in place of the NSs gene [51], and a wt RVFV-derived avirulent mutant lacking NSs and NSm genes, both of which are viral virulence factors [52]–[55], demonstrated excellent protective immunogenicity against wt RVFV after a single immunization of animals [56].…”

Advances and perspectives in the development of vaccines against highly pathogenic bunyaviruses

“…To improve on this candidate, the United States Army Medical Research Institute of Infectious Diseases developed an inactivated RVFV vaccine by FRhL-2 cells called TSI-GSD-200 ( Faburay et al., 2017 ). From its Phase I clinical trial results, although TSI-GSD-200 has better immunogenicity, mild and transient local reactions were still present, ranging from 5% at the lowest dose level to 43% at the highest, indicating safety concerns if the vaccine was to be administered to a larger population ( Kark et al., 1982 ). Interestingly, there are long-lived RVFV-specific T-cell responses detected in volunteers vaccinated with the formalin-inactivated RVFV vaccine, suggesting that T-cell immunity may play a role in protection from RVFV infection ( Harmon et al., 2020 ).…”

Novel approaches to develop Rift Valley fever vaccines

“…The formalin-inactivated Salk Institute-Government Services Division (TSI-GSD)-200 vaccine was developed by using diploid rhesus lung cell line (FRhL-2, DBS 103 cells) (Kark et al, 1982). Among 598 vaccinees, TSI-GSD-200 vaccine elicited Plaque Reduction Neutralizing Test: PRNT 80 1:40 or more in 90.3% after three doses (s.c.), while PRNT 80 1:40 was maintained in 50% of vaccines only for 287 days without subsequent boosters (Pittman et al, 2000).…”