Immunogenicity and protective efficacy of human metapneumovirus virus-like particles produced by a recombinant baculovirus in mice

Fenlian Ma; Aijun Chen; Lihong Yao; Hanchun Gao; Qian Zhang; Wenzhe Hou; Lishu Zheng

doi:10.1016/j.virusres.2023.199215

Immunogenicity and protective efficacy of human metapneumovirus virus-like particles produced by a recombinant baculovirus in mice

Virus Res. 2023 Oct 15:336:199215. doi: 10.1016/j.virusres.2023.199215. Epub 2023 Sep 2.

Authors

Fenlian Ma¹, Aijun Chen¹, Lihong Yao¹, Hanchun Gao¹, Qian Zhang¹, Wenzhe Hou¹, Lishu Zheng²

Affiliations

¹ NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, 100 Ying-Xin St., Xi-Cheng District, Beijing 100052, China.
² NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, 100 Ying-Xin St., Xi-Cheng District, Beijing 100052, China. Electronic address: zhengls@ivdc.chinacdc.cn.

Abstract

Background: Human metapneumovirus (HMPV) causes respiratory tract infections among infant, elderly, and immunocompromised patients, with significant mortality. Currently no licensed vaccines or therapeutic agents of HMPV exist.

Methods: HMPV virus-like particle (VLP) was constructed by co-expressing fusion protein of HMPV and matrix 1 protein of influenza virus using the baculovirus expression. Mice were immunized with VLP with or without aluminum hydroxide (alum) adjuvant by intramuscular route respectively. Sera were determined for titers of IgG and neutralizing antibody. Splenic lymphocytes were determined by IFN-γ and IL-4 ELISPOT. Mice were challenged with HMPV, and protective efficacy was evaluated.

Results: We generated HMPV VLP in baculovirus expression system. After three times immunization, IgG antibody titers induced by VLP formulated with or without alum adjuvant group were 273,066 ± 100,331 and 136,533 ± 47,269 respectively, there was no difference (p ˃ 0.05); the neutralizing antibody titers vaccinated with VLP plus with alum adjuvant (266 ± 92) were higher than those of the VLP alone group (106 ± 37). For IFN-γ, mice vaccinated with VLP with or without alum adjuvant are 151 ± 36.4 and 77.0 ± 17.1SFC/10⁶ respectively, there was difference (p = 0.03); For IL-4, they are 261.3 ± 38.7 versus 125.67 ± 29.78SFC/10⁶ respectively, the difference was significant (p = 0.009). After challenge, in pathological analysis, the overall lesion scores in the VLP plus with and without alum adjuvant were 3.25 and 5.6 respectively, those of control group is 8. For immunohistochemical analyses, the average optical density of the lungs in the VLP immunized group containing adjuvant (9.07 ± 1.74) was lower than that in the VLP group without adjuvant (12.83 ± 2.31, p = 0.14).

Conclusions: This is the first study to demonstrate that HMPV VLP was successfully prepared in the baculovirus expression system. HMPV VLP could induce specific humoral and cellular immune responses as well as protective efficacy, and aluminum hydroxide may be an effective adjuvant in mice.

Keywords: Human metapneumovirus; Immunogenicity; Protective efficacy; Virus-like particle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / genetics
Aged
Aluminum Hydroxide
Animals
Antibodies, Neutralizing
Antibodies, Viral
Baculoviridae / genetics
Humans
Interleukin-4
Metapneumovirus* / genetics
Mice
Mice, Inbred BALB C
Vaccines, Virus-Like Particle* / genetics

Substances

aluminum sulfate
Antibodies, Viral
Aluminum Hydroxide
Interleukin-4
Antibodies, Neutralizing
Adjuvants, Immunologic
Vaccines, Virus-Like Particle