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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Experimental infection of macaques with human metapneumovirus induces transient protective immunity
Bernadette G van den Hoogen1, Sander Herfst1, Miranda de Graaf1
1Department of Virology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Abstract:
Human metapneumovirus (hMPV), a member of the family Paramyxoviridae, is a causative agent of acute respiratory-tract illness. Two main hMPV lineages circulate worldwide and reinfections occur frequently. It is unclear what level of protection is induced by natural hMPV infection, what the durability of this protection is and whether it differs for reinfection with homologous or heterologous viruses. Here, protective immunity in cynomolgus macaques at different time points after inoculation with molecularly cloned prototype viruses of the two main lineages of hMPV has been addressed. Animals received a homologous challenge at 4, 6 or 12 weeks after the primary infection. In addition, animals that had been inoculated three times within 10 weeks were challenged with homologous or heterologous virus 8 months later. Primary infection with 10(7) TCID(50) resulted in virus shedding and induction of virus-neutralizing antibody responses, with higher titres against the homologous than the heterologous virus. Infections associated with virus shedding and seroconversion protected completely from homologous reinfection within 6 weeks, and partly at 12 weeks, after primary infection. Eight months later, protection had waned to virtually undetectable levels. This study demonstrates that experimental hMPV infection induces transient protective immunity.
Insights
Natural human metapneumovirus (hMPV) infection provides temporary protection against reinfection. Immunity wanes significantly within months, indicating transient protective immunity following hMPV illness.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Human metapneumovirus (hMPV), a Paramyxoviridae family member, causes acute respiratory illness.
- Two primary hMPV lineages circulate globally, leading to frequent reinfections.
- The duration and effectiveness of immunity following natural hMPV infection remain unclear.
Purpose of the Study:
- To investigate the protective immunity induced by experimental hMPV infection in cynomolgus macaques.
- To assess the durability of protection against homologous and heterologous hMPV reinfection at various time points.
- To understand the impact of primary infection on subsequent viral shedding and antibody responses.
Main Methods:
- Cynomolgus macaques were inoculated with prototype hMPV viruses from the two main lineages.
- Animals received homologous viral challenges at 4, 6, and 12 weeks post-primary infection.
- A separate group received multiple inoculations and was challenged with homologous or heterologous virus 8 months later.
Main Results:
- Primary hMPV infection induced virus shedding and neutralizing antibody responses, with higher titers against homologous strains.
- Complete protection from homologous reinfection occurred within 6 weeks, partial protection at 12 weeks.
- Protection waned to undetectable levels by 8 months post-infection, regardless of prior homologous or heterologous exposure.
Conclusions:
- Experimental hMPV infection induces transient protective immunity in macaques.
- The level and durability of protection decrease significantly over time.
- Further research is needed to understand long-term immunity and vaccine strategies for hMPV.
