Passive Immunization Protects Cynomolgus Macaques against Puumala Hantavirus Challenge

Abstract

Background

Hantaviruses cause two severe and often fatal human diseases: haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Presently, there is no effective prevention available for HFRS or HPS. Here, we studied the effect of passive immunization on the course of infection in cynomolgus macaques challenged with wild-type Puumala hantavirus (PUUV-wt).

Methods

A pool of serum drawn from previously PUUV-wt-infected monkeys was used for immunization; a pool of serum from the same monkeys that was obtained before infection was used as a control. Immunizations were administered 3 days before and 15 days after challenge with PUUV-wt. After challenge, monkeys were sampled once a week and analysed for PUUV-infection markers.

Results

All three monkeys treated with non-immune serum became positive for PUUV RNA in plasma and showed PUUV nucleocapsid-specific immunoglobin M (IgM) responses after challenge. In contrast, no PUUV RNA or anti-PUUV-specific IgM response was detected in the three passively immunized monkeys. As seen in PUUV-infected humans, the control monkeys showed a marked decrease in the amount of platelets and increased levels of creatinine, interleukin (IL)-6, IL-10, and tumour necrosis factor (TNF) after inoculation. In contrast, no marked changes in the amount of platelets were observed in the immunized monkeys and they did not show increased levels of creatinine, IL-6, IL-10 and TNF after virus challenge.

Conclusion

The results show that passive immunization in monkeys, using serum from previously hantavirus-infected monkeys, can induce sterile protection and protect against pathogenesis. Convalescent-phase antibodies may represent a potential therapy that can induce immediate protection against HFRS and HPS.