Inactivated Lassa virus elicits a non protective immune response in rhesus monkeys

Abstract

We attempted to protect three rhesus monkeys from Lassa fever by vaccination with a preparation of purified whole Lassa virus which had been inactivated by gamma irradiation. The vaccinated monkeys developed antibodies against the three major viral proteins of Lassa virus demonstrated by radioimmunoprecipitation. When the three vaccinated monkeys and two unvaccinated control monkeys were challenged all five became severely ill and died. Prior to death a secondary, high-titer antibody response to Lassa virus was observed in the three vaccinated monkeys, whereas the two unvaccinated monkeys developed a primary, low-titer antibody response. Though titers of Lassa virus in serum reached peak levels earlier following challenge in the non vaccinated, at the time of death serum and organ virus titers did not differ significantly. Changes in platelet aggregation, leukocyte counts, and liver enzymes, abnormalities of which have been associated with severity of Lassa fever, were found to be comparable in the two groups. The humoral antibody response measured in these animals following vaccination, although of the same magnitude as found in humans recovered from Lassa fever, was insufficient to protect the animals from this fatal disease. Evidence is now accumulating that the cell-mediated immune response must be activated in order to protect against challenge with arenaviruses.

Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

“…However, after challenge all the monkeys showed viremia and died. The inactivated Lassa virus vaccine based on gamma irradiation could not protect the animals after challenge [97].…”

“…This inactivation procedure has been investigated for FMDV, Rauscher leukemia virus, HSV [96] and Lassa virus (Table 8) [97]. Inactivation kinetics showed that Rauscher leukemia virus and HSV were inactivated at a dose of 25 kGy.…”

The nucleoprotein of Pichinde virus expressed by a vaccinia-Pichinde virus recombinant partially protects hamsters from lethal virus challenge

“…Development of vaccines against Lassa virus and Junin virus demonstrate the requirement for cellular immunity. Inactivated Lassa virus used in primates was able to induce antibodies against the nucteoprotein and glycoproteins, but not anti-Lassa cellular responses, and could not protect against Lassa infection [21]. Similarly inactivated XJ-clone 3 of Junin virus used as a vaccine in guinea pigs generated antibodies but was not protective [33], but priming guinea pigs or monkeys with live-attenuated Junin virus, produced protective immune responses [22,33].…”

Dose-Response Model for Lassa Virus

“…Lange et al (1985) subcutaneously injected 3000 PFU (Plaque Forming Unit) to Rhesus monkeys to find out the effect of virus in different organs of the monkeys. McCormick et al (1992) experimented with 10 4 PFU Lassa virus subcutaneously injected to inactivated viral vaccinated Rhesus monkeys. In experiments performed by Lukashevich et al (2005), inbred guinea pigs and rhesus monkeys were inoculated with cloned MOPV (Mopeia virus) and ML29 (mixture of RNA from MOPV and Lassa Virus ) then challenged with a Lassa virus of dose 10 3 PFU.…”