A Rift Valley fever vaccine trial: 2. Serological response to booster doses with a comparison of intradermal versus subcutaneous injection.

A booster dose of a formalin-inactivated, cell culture-propagated Rift Valley fever vaccine (TSI-GSD-200) was administered without significant reactogenicity to 60 volunteers 18 months after they received a three dose primary series. Blood was drawn for serological testing prior to boosting and 10, 49, and 180 days thereafter. Neutralizing antibody response was prompt, being maximum on day 10 and considerably higher than the peak titres obtained on day 42 after the initial series. A marked decline in antibody titres was evident by day 180, as seen for the primary series, but residual titres were substantially higher. The initial series was given in doses of 1.0, 0.5, 0.3, or 0.1 ml and the immune status achieved with these injections was a major determinant of the response to boostering. Secondary responses were highly dependent in magnitude and duration on the prior immune status of the recipient. Evaluation of dose and route of recall inoculation showed 1.0 ml given subcutaneously (SC) to be equivalent to 0.1 ml administered intradermally (ID), though inference should be guarded due to the small sample size. Although 0.1 ml SC dose was inferior to either, it was modestly effective. Intradermal administration of vaccine may be useful for extending the small reserve of vaccine available for use in emergency.

A rift Valley fever vaccine trial. I. Side effects and serologic response over a six-month follow-up.

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.

A serological survey of Rift Valley fever antibodies in the northern Sinai.

In the aftermath of an extensive Egyptian Rift Valley fever (RVF) epidemic during 1977-78, RVF activity in the adjacent Sinai peninsula has been inferred from the presence of haemagglutination-inhibition (HI) antibodies in sera from indigenous humans and rodents. We attempted to confirm these findings by HI testing of sera from Israeli soldiers serving in the region of the El Arish Wadi system in the Sinai, and from indigenous rodents. Six of 199 human sera (3.0%) and two of 88 rodent sera (2.3%) were positive, but none reacted in the more specific plaque-reduction neutralization test. We conclude that there is no definitive serological evidence for RVF activity in the Sinai and that sera reacting in the HI test must be confirmed by a more specific serological procedure.