• Vaccine Ontology ID: VO_0004378
• Type: Recombinant vector vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Macaque
• LASVsSgp2 glycoprotein gene engineering:
  • Type: Recombinant vector construction
  • Description: Vector NYBH strains of vaccinia virus expressed the uncleaved, full-length glycoprotein (Fisher-Hoch et al., 2000).
  • Detailed Gene Information: Click Here.
• Vector: NYBH strains of vaccinia virus (Fisher-Hoch et al., 2000)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004379
• Type: Recombinant vector vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Macaque
• LASVsSgp1 nucleoprotein gene engineering:
  • Type: Recombinant vector construction
  • Description: Vector NYBH strains of vaccinia virus expressed the nucleoprotein (Fisher-Hoch et al., 2000).
  • Detailed Gene Information: Click Here.
• LASVsSgp2 glycoprotein gene engineering:
  • Type: Recombinant vector construction
  • Description: Vector NYBH strains of vaccinia virus expressed the glycoprotein (Fisher-Hoch et al., 2000).
  • Detailed Gene Information: Click Here.
• Vector: NYBH strains of vaccinia virus (Fisher-Hoch et al., 2000)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004085
• Type: Attenuated
• Preparation: Clone ML29 is selected and triple plaque purified. The viruses are grown on Vero E6 cells cultured in Dulbecco's modified minimum Eagle's medium with 2% fetal calf serum, 1% penicillin-streptomycin, and l-glutamine (2 mM) at 37°C in 5% CO2. Cells and virus stocks were free of mycoplasma contamination (Lukashevich et al., 2005).
• Description: ML29 is a clone that has been isolated from a Mopeia virus (MOPV) and Lassa virus (LASV) reassortant. It contains the L RNA from MOPV and the S RNA segment from LASV (Lukashevich et al., 2005).

• Vaccine Ontology ID: VO_0004080
• Type: Vaccina virus
• Preparation: The sequence is derived from the Josiah strain of Lassa virus, isolated from a patient in Sierra Leone (Fisher-Hoch et al., 2000).
• Virulence:
• Description: V-LSG is a vaccinia viruses expressing the S-segment Lassa glycoprotein (Fisher-Hoch et al., 2000).

• Vaccine Ontology ID: VO_0004082
• Type: Vaccina virus
• Preparation: Each sequence is derived from the Josiah strain of Lassa virus, isolated from a patient in Sierra Leone (Fisher-Hoch et al., 2000).
• Virulence:
• Description: V-LSG is a vaccinia viruses expressing the S-segment Lassa glycoprotein and V-LSN is a vaccinia viruses expressing the S-segment Lassa nucleoprotein. V-LSG + V-LSN is a vaccine that includes injections of each V-LSG and V-LSN separately (Fisher-Hoch et al., 2000).

• Vaccine Ontology ID: VO_0004083
• Type: Vaccina virus
• Preparation: V-LSG is a vaccinia viruses expressing the S-segment Lassa glycoprotein (Fisher-Hoch et al., 2000).
• Virulence:
• Description: V-LSG/N is a vaccinia viruses expressing the full length glycoprotein and nucleoprotein in the same construct (Fisher-Hoch et al., 2000).

• Vaccine Ontology ID: VO_0004081
• Type: Vaccina virus
• Preparation: The sequence is derived from the Josiah strain of Lassa virus, isolated from a patient in Sierra Leone (Fisher-Hoch et al., 2000).
• Virulence:
• Description: V-LSG1 + V- LSG2 is a vaccinia viruses expressing the S-segment Lassa single glycoproteins V-LSG1 [containing residues 1 to 296] and V-LSG2 [with a deletion of residues 67 to 234] (Fisher-Hoch et al., 2000).

• Vaccine Ontology ID: VO_0004079
• Type: Vaccina virus
• Preparation: The sequence is derived from the Josiah strain of Lassa virus, isolated from a patient in Sierra Leone (Fisher-Hoch et al., 2000).
• Virulence:
• Description: V-LSN is a vaccinia viruses expressing the S-segment Lassa nucleoprotein (Fisher-Hoch et al., 2000).

• Vaccine Ontology ID: VO_0004087
• Type: Live Attenuated
• LASVsSgp2 glycoprotein gene engineering:
  • Type: Protein
  • Detailed Gene Information: Click Here.
• Preparation: The recombinant VSV expressing the glycoprotein of Lassa virus, strain Josiah, and Zaire ebolavirus (ZEBOV), strain Mayinga, were generated using the infectious clone for the VSV, Indiana serotype. Briefly, the appropriate open reading frames for the glycoproteins were generated by PCR, cloned into the VSV genomic vectors lacking the VSV glycoprotein gene, sequenced-confirmed, and rescued. The recombinant viruses expressing Lassa virus glycoprotein and ZEBOV glycoprotein were designated VSV[Delta]G/LVGPC (Figure 1A) and VSV[Delta]G/ZEBOVGP, respectively (Geisbert et al., 2005).
• Virulence:
• Description: VSV[Delta]G/LVGPC ia a live attenuated recombinant vesicular stomatitis virus expressing the GPC of Lassa virus, strain Josiah. Vaccines based on live attenuated rVSV have been highly effective in animal models and are particularly attractive because they can be administered by the mucosal route (Geisbert et al., 2005).

Monkey Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: The protection of our animals by Lassa virus glycoprotein expressed in vaccinia virus in the face of a low antibody response supports that antibody alone does not provide protection. Proper folding of LCMV glycoprotein is critical for induction of the humoral response and vaccinia virus-expressed glycoproteins are not posttranslationally processed or transported correctly to the membrane. Thus, the minimal measurable antibody response to glycoprotein after vaccination may be related to improperly folded glycoprotein (Fisher-Hoch et al., 2000).
• Efficacy: 8 of 9 V-LSG-vaccinated animals survived Lassa virus challenge (Fisher-Hoch et al., 2000).

Monkey Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: The protection of our animals by Lassa virus glycoprotein expressed in vaccinia virus in the face of a low antibody response supports that antibody alone does not provide protection. Proper folding of LCMV glycoprotein is critical for induction of the humoral response and vaccinia virus-expressed glycoproteins are not posttranslationally processed or transported correctly to the membrane. Thus, the minimal measurable antibody response to glycoprotein after vaccination may be related to improperly folded glycoprotein (Fisher-Hoch et al., 2000).
• Efficacy: 9 of 10 monkeys that received the V-LSG/N vaccine survived challenge with Lassa virus (Fisher-Hoch et al., 2000).

Monkey Response

• Host Strain: Rhesus macaques
• Vaccination Protocol: Two adult rhesus macaques were s.c. injected with 10^3 PFU of ML29. Blood samples were taken weekly and submitted to the clinical laboratory for complete blood counts and standard 20-assay chemistry panels. At days 14 and 28, the monkeys were euthanized and total blood and tissues were collected. A portion of each tissue was submerged in MEM with 10% FCS (for plaque titration) and in RNAlater (for RNA isolation). The remaining tissue portions were fixed in 10% neutral formalin for the preparation of standard histological sections and stained with hematoxylin-eosin (Lukashevich et al., 2005).
• Efficacy: This data indicates that ML29 vaccination of rhesus macaques results in a short, inapparent, self-limited infection (Lukashevich et al., 2005).
• Description: The ML29-vaccinated animals were afebrile throughout the experiment and had no clinical manifestations. Hematological and chemical parameters were in the normal ranges, as was gross appearance at necropsy. Detailed histological examination of rhesus macaques infected with the ML29 reassortant revealed no tissue lesions. The ML29 virus replicated poorly in monkeys and was not detectable in the plasma and tissues by conventional infectious plaque assay. The only organ from which the virus was recovered was the spleen. RT/PCR with LASV GPC-derived primers was transiently positive with RNA plasma and tissue samples (Lukashevich et al., 2005).

Monkey Response

• Host Strain: Rhesus and Cynomolgus
• Vaccination Protocol: All animals received a single vaccination consisting of 0.2 ml of vaccine given intradermally and simultaneously at four separate sites (each forearm and the lateral aspect of each thigh) at a dilution which delivered to each animal a total dose of 10^9 PFU. All animals were challenged subcutaneously with 10^3 to 10^4 PFU of the Josiah strain of Lassa virus in 0.5 ml of phosphate-buffered saline within 36 to 700 days (Fisher-Hoch et al., 2000).
• Persistence: The latest day on which virus could be recovered from serum was day 14, and that from tissues was day 21. Evidence for persistence elsewhere in tissues or fluids in survivors could not be found by cocultivation of tissues taken up to 112 days following challenge. However, autopsy and biopsy material examined by RT-PCR revealed that viral RNA could be detected at least 112 days after challenge (Fisher-Hoch et al., 2000).
• Side Effects: Animals showed little or no disturbance of liver function, even in the face of viremia (Fisher-Hoch et al., 2000).
• Efficacy: The response to glycoprotein protects these animals from induction of fatal processes leading to disease and death (Fisher-Hoch et al., 2000).
• Description: 8 of 9 vaccinated animals survived. This protection against death was significant when compared with the death rate of the controls. These animals showed significantly diminished mean virus titers compared with those of unvaccinated animals. The one V-LSG-vaccinated animal that died reached maximum viremia on day 8, and the last day on which virus was detected in serum was day 11. The animal the died was the one with the longest vaccine-to-challenge interval. Survival diminished as the vaccine-to-challenge interval increased. A trend towards increasing duration of viremia was also observed with increased intervals between vaccination and challenge (Fisher-Hoch et al., 2000).

Monkey Response

• Host Strain: Rhesus and Cynomolgus
• Vaccination Protocol: All animals received a single vaccination consisting of 0.2 ml of vaccine given intradermally and simultaneously at four separate sites (each forearm and the lateral aspect of each thigh) at a dilution which delivered to each animal a total dose of 10^9 PFU. All animals were challenged subcutaneously with 10^3 to 10^4 PFU of the Josiah strain of Lassa virus in 0.5 ml of phosphate-buffered saline within 36 to 700 days (Fisher-Hoch et al., 2000).
• Persistence: The latest day on which virus could be recovered from serum was day 14, and that from tissues was day 21. Evidence for persistence elsewhere in tissues or fluids in survivors could not be found by cocultivation of tissues taken up to 112 days following challenge. However, autopsy and biopsy material examined by RT-PCR revealed that viral RNA could be detected at least 112 days after challenge (Fisher-Hoch et al., 2000).
• Side Effects: None noted
• Efficacy: When used together, V-LSG and V-LSN can provide sufficient means for protection against Lassa fever (Fisher-Hoch et al., 2000).
• Description: 5 out of 6 of the monkeys survived. This protection against death was significant when compared with the death rate of the controls. These animals showed significantly diminished mean virus titers compared with those of unvaccinated animals. The animal the died was the one with the longest vaccine-to-challenge interval. Survival diminished as the vaccine-to-challenge interval increased. A trend towards increasing duration of viremia was also observed with increased intervals between vaccination and challenge (Fisher-Hoch et al., 2000).

Monkey Response

• Host Strain: Rhesus
• Vaccination Protocol: Two animals were vaccinated. Each animal received a single vaccination consisting of 0.2 ml of vaccine given intradermally and simultaneously at four separate sites (each forearm and the lateral aspect of each thigh) at a dilution which delivered to each animal a total dose of 10^9 PFU. All animals were challenged subcutaneously with 10^3 to 10^4 PFU of the Josiah strain of Lassa virus in 0.5 ml of phosphate-buffered saline within 36 to 700 days
• Persistence: The latest day on which virus could be recovered from serum was day 14, and that from tissues was day 21. Evidence for persistence elsewhere in tissues or fluids in survivors could not be found by cocultivation of tissues taken up to 112 days following challenge. However, autopsy and biopsy material examined by RT-PCR revealed that viral RNA could be detected at least 112 days after challenge (Fisher-Hoch et al., 2000).
• Side Effects: None noted
• Efficacy: The results of this experiment show that V-LSG/N provides effective means of protecting monkeys against the Lassa virus (Fisher-Hoch et al., 2000).
• Description: Both of the animals survived when challenged with the Lassa virus. These animals showed no significant mean virus titers when compared with those of unvaccinated animals (Fisher-Hoch et al., 2000).

Monkey Response

• Host Strain: Rhesus
• Vaccination Protocol: All animals received a single vaccination consisting of 0.2 ml of vaccine given intradermally and simultaneously at four separate sites (each forearm and the lateral aspect of each thigh) at a dilution which delivered to each animal a total dose of 10^9 PFU. Each vaccine was administered in one arm and one leg on the ipsilateral side. All animals were challenged subcutaneously with 10^3 to 10^4 PFU of the Josiah strain of Lassa virus in 0.5 ml of phosphate-buffered saline within 36 to 700 days (Fisher-Hoch et al., 2000).
• Persistence: The latest day on which virus could be recovered from serum was day 14, and that from tissues was day 21. Evidence for persistence elsewhere in tissues or fluids in survivors could not be found by cocultivation of tissues taken up to 112 days following challenge. However, autopsy and biopsy material examined by RT-PCR revealed that viral RNA could be detected at least 112 days after challenge (Fisher-Hoch et al., 2000).
• Side Effects: None noted
• Efficacy: Although V-LSG1 and V-LSG2 do not provide sufficient protection by themselves, when used together the can provide protective immunity to primates. This means that both glycoproteins are independently important in Lassa virus protection (Fisher-Hoch et al., 2000).
• Description: Both of the monkeys vaccinated with V-LSG1 + V-LSG2 were protected when challenged Lassa virus (Fisher-Hoch et al., 2000).

Monkey Response

• Host Strain: Rhesus and Cynomolgus
• Vaccination Protocol: All animals received a single vaccination consisting of 0.2 ml of vaccine given intradermally and simultaneously at four separate sites (each forearm and the lateral aspect of each thigh) at a dilution which delivered to each animal a total dose of 10^9 PFU. All animals were challenged subcutaneously with 10^3 to 10^4 PFU of the Josiah strain of Lassa virus in 0.5 ml of phosphate-buffered saline within 36 to 700 days (Fisher-Hoch et al., 2000).
• Persistence: The latest day on which virus could be recovered from serum was day 14, and that from tissues was day 21. Evidence for persistence elsewhere in tissues or fluids in survivors could not be found by cocultivation of tissues taken up to 112 days following challenge. However, autopsy and biopsy material examined by RT-PCR revealed that viral RNA could be detected at least 112 days after challenge (Fisher-Hoch et al., 2000).
• Side Effects: Monkeys had marked lymphopenia and higher mean aspartate aminotransferase values than unvaccinated animals. The V-LSN-vaccinated animals were observed to be sicker and died earlier than unvaccinated animals (Fisher-Hoch et al., 2000).
• Efficacy: Vaccination using the nucleoprotein may protect primates against a lower challenge dose of Lassa virus, however, the V-LSN vaccine was not significantly protective (Fisher-Hoch et al., 2000).
• Description: 8 of the 11 vaccinated animals died, which shows that this vaccine was not significantly protective. The V-LSN animals appeared to have a shorter and more acute process than unprotected animals. The median day of death for V-LSN animals was day 11.5, compared with day 13 for the control animals. This phenomenon was related to the challenge dose. Back titration of the challenge inoculum used in the final experiment showed that the titer had dropped from 10^4 to 10^3 PFU/ml. The three V-LSN-vaccinated animals in that experiment that received the lower challenge titer survived. These three animals were rhesus monkeys (Fisher-Hoch et al., 2000).

Monkey Response

• Host Strain: Cynomolgus macaques
• Vaccination Protocol: Four cynomolgus macaques, 4–6 y old and weighing between 3 kg and 8 kg, were vaccinated intramuscularly with approximately 2 × 10^7 PFU of VSV[Delta]G/LVGPC, and two with an equivalent dose of VSV[Delta]G/ZEBOGP (controls). The six cynomolgus macaques were challenged intramuscularly 28 d after the single-dose immunization with 1 × 10^4 plaque-forming units of Lassa virus, Josiah strain (Geisbert et al., 2005).
• Persistence: None noted
• Side Effects: After vaccination, none of the nonhuman primates displayed any signs of clinical symptoms, indicating that the rVSVs were apathogenic for these animals (Geisbert et al., 2005).
• Efficacy: The VSV-based vector expressing the Lassa virus GPC mediated complete protection of four of four cynomolgus monkeys from a high-dose lethal challenge of Lassa virus. Protection was associated with the generation of Lassa-specific CD8+ T cell and antibody responses. The primary concern regarding use of the rVSV vaccine platform in humans is related to the fact that this is a replication-competent vaccine, and thus demonstration of safety is of paramount importance (Geisbert et al., 2005).
• Description: After the challenge, the two control animals started to show clinical signs of illness on day 3, when one of the animals had a fever. By day 10, both control animals developed macular rashes and anorexia, and one animal had severe facial edema, which is prognostic for a poor outcome in humans. These control animals succumbed to the Lassa virus challenge and were euthanized on day 11 and day 13. At necropsy, both controls showed lesions and pathological changes consistent with Lassa fever in nonhuman primates. In contrast, none of the vaccinated animals became sick, and all four animals were fully protected against the high Lassa challenge dose. By day 7 after challenge, all six monkeys were viremic. However by day 10, all four of the vaccinated animals had cleared the viremia, while both control animals had high viremias, which was maintained until euthanasia (Geisbert et al., 2005).

Guinea pig Response

• Host Strain: 13
• Vaccination Protocol: Ten animals were inoculated subcutaneously (s.c.) with the ML29 clone, and 10 guinea pigs received the same dose of MOPV. Eight animals were used as negative controls. At day 30 after vaccination, the animals were s.c. challenged with 10^3 PFU of LASV (Josiah) and followed for 70 days. Liver enzymes were measured in plasma. Vaccinated animals were euthanized on day 70 after challenge, and tissues were removed (Lukashevich et al., 2005).
• Persistence: None noted
• Side Effects: In vaccinated animals, LASV infection did not induce alterations in target tissues. The lungs and livers of vaccinated animals looked essentially like normal tissues. There were also no lesions in other major organs (Lukashevich et al., 2005).
• Efficacy: All strain 13 guinea pigs vaccinated with clone ML29 survived at least 70 days after LASV challenge without either disease signs or histological lesions (Lukashevich et al., 2005).
• Description: Infection of strain 13 guinea pigs with MOPV or with the ML29 reassortant was not lethal for the animals and did not induce clinical or biochemical signs of the disease. All animals survived after challenge and had no clinical manifestations. All measured parameters were in normal ranges in ML29-vaccinated guinea pigs. In MOPV-vaccinated animals, a transient elevation of AST and AlkPh in plasma was observed at week 3 after challenge (Lukashevich et al., 2005).