• Vaccine Name: Lassa fever virus vaccine ChAdOx1-Lassa-GPC
• Target Pathogen: Lassa Fever Virus
• Target Disease: Lassa fever
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Antigen: Josiah Strain Lassa Virus glycoprotein precursor (GPC) (Fischer et al., 2021)
• Immunization Route: Intramuscular injection (i.m.)

Guinea pig Response

• Vaccination Protocol: Three groups of animals (n = 10 per group) received the following immunizations: 3.0 × 10^8 IU of ChAdOx1-Lassa-GPC on D-56 and D-28 (prime-boost), 3.0 × 10^8 IU of ChAdOx1-Lassa-GPC on D-28 (prime), or 1.0 × 10^8 IU of ChAdOx1-GFP on D-28 (control). (Fischer et al., 2021)
• Immune Response: Despite conferring 100% protection against clinical disease after LASV challenge, vaccination with ChAdOx1-Lassa-GPC did not induce sterile immunity. Low amounts of LASV RNA were detected in the tissues of immunized animals necropsied on D12 by qRT-PCR. In the lungs, mean differences (±SEM) in viral load between the control animals and prime-boost or prime vaccinates were 6.99 ± 0.68 and 6.90 ± 0.68 log TCID50/g equivalents, respectively. Similarly, mean viral loads in the livers of control animals exceeded that of animals in the prime-boost and prime groups by 5.46 ± 0.68 and 4.83 ± 0.68 log TCID50/g equivalents, respectively. Finally, vaccination with ChAdOx1-Lassa-GPC reduced splenic viral load by 5.94 ± 0.68 and 5.61 ± 0.68 log TCID50/g equivalents after prime-boost or single-dose delivery, respectively. Reductions in viral RNA in the vaccinated animals versus controls were statistically significant for all tissues (p < 0.0001, two-way ANOVA with Tukey’s multiple comparisons test). Meanwhile, no significant differences were observed between the prime-boost and prime immunization groups. Antibody responses specific to LASV nucleoprotein (NP) were mounted in vaccinated and control animals by D12, which further suggested that low-level virus replication occurred (mean ± SEM ELISA titer: prime-boost = 1500 ± 619, prime = 24000 ± 9906, control = 20800 ± 4800). The titer of anti-NP IgG antibodies was significantly lower in animals receiving prime-boost vaccination compared to those receiving a single dose or control vaccination (p = 0.0492, Kruskal–Wallis nonparametric test with Dunn’s multiple comparisons). No viable LASV was isolated from the tissues of any of the animals immunized with ChAdOx1-Lassa-GPC, besides a single lung sample from an animal in the prime vaccination group (2.52 log TCID50/g) at just above the limit of detection of the assay. Meanwhile, infectious virus was detected in all tissues isolated from control animals (mean ± SEM in lung, liver, spleen: 7.58 ± 0.31, 6.77 ± 0.31, 7.15 ± 0.26 log TCID50/g). Differences in mean virus titer between prime-boost vaccinates and controls (lung, liver, spleen: p = 0.0008, 0.0012, 0.0006), as well as between prime vaccinates and controls (lung, liver, spleen: p = 0.0002, 0.0012, 0.0006) were statistically significant (two-way ANOVA with Tukey’s multiple comparisons test). (Fischer et al., 2021)
• Challenge Protocol: On D0, all animals were challenged with 1.0 × 105 TCID50 of GPA-Josiah strain LASV, which was passaged four times in Hartley guinea pigs. GPA LASV harbors a single nucleotide polymorphism in the S genomic segment compared to the wild-type Josiah strain virus. (Fischer et al., 2021)
• Efficacy: On D12 post challenge, four randomly selected animals from each group were euthanized to perform virological assessments in lung, liver, spleen, and sera. The remaining animals were used to assess survival; animals in the survival cohort were euthanized after meeting humane endpoint criteria or on D-28 post challenge, which marked the study endpoint. All survival cohort guinea pigs vaccinated with ChAdOx1-Lassa-GPC survived challenge and did not develop fevers, experience weight loss, or exhibit other signs of disease. No discernable differences in weight or temperature were observed between prime and prime-boost vaccinates. By contrast, all control animals in the survival cohort developed signs of terminal illness and met humane endpoint criteria (>20% weight loss) on or before D12. The temperatures of control animals began to increase on D3 and animals became febrile by D8. Weight loss was observed by D7 and progressed until euthanasia by D12. (Fischer et al., 2021)