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A Broadly Cross-protective Vaccine Presenting the Neighboring Epitopes within the VP1 GH Loop and VP2 EF Loop of Enterovirus 71.

Xu L, He D, Yang L, Li Z, Ye X, Yu H, zhao H, Li S, Yuan L, Qian H, Que Y, Shih JW, Zhu H, Li Y, Cheng T, Xia N - Sci Rep (2015)

Bottom Line: We demonstrate that anti-VP2 (aa141-155) sera bound authentic CA16 viral particles, whereas anti-VP1 (aa208-222) sera could not.Moreover, the anti-VP2 (aa141-155) antibodies inhibited the binding of human serum to virions, which demonstrated that the VP2 epitope is immunodominant between EV71 and CA16.These results illustrated that the chimeric VLP HBc-E1/2 is a promising candidate for a broad-spectrum HFMD vaccine, and also reveals mechanisms of protection by the neighboring linear epitopes of the VP1 GH and VP2 EF loops.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen 361102, PR China.

ABSTRACT
Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major etiological agents of hand, foot and mouth disease (HFMD) and are often associated with neurological complications. Currently, several vaccine types are being developed for EV71 and CA16. In this study, we constructed a bivalent chimeric virus-like particle (VLP) presenting the VP1 (aa208-222) and VP2 (aa141-155) epitopes of EV71 using hepatitis B virus core protein (HBc) as a carrier, designated HBc-E1/2. Immunization with the chimeric VLPs HBc-E1/2 induced higher IgG titers and neutralization titers against EV71 and CA16 in vitro than immunization with only one epitope incorporated into HBc. Importantly, passive immunization with the recombinant HBc-E2 particles protected neonatal mice against lethal EV71 and CA16 infections. We demonstrate that anti-VP2 (aa141-155) sera bound authentic CA16 viral particles, whereas anti-VP1 (aa208-222) sera could not. Moreover, the anti-VP2 (aa141-155) antibodies inhibited the binding of human serum to virions, which demonstrated that the VP2 epitope is immunodominant between EV71 and CA16. These results illustrated that the chimeric VLP HBc-E1/2 is a promising candidate for a broad-spectrum HFMD vaccine, and also reveals mechanisms of protection by the neighboring linear epitopes of the VP1 GH and VP2 EF loops.

No MeSH data available.


Related in: MedlinePlus

In vivo cross-protection of HBc-E1/2 to EV71 and CA16.(A) Groups of one-day old BALB/c mice born to female mice immunized with HBc-E1/2, HBc-E1, HBc-E2 or adjuvant with an immunization dose of 100 μg were challenged with pSVA-MP4 or CA16-190. The mortality were monitored and recorded daily for 20 days. The representative results of two independent experiments are shown. (B) Contrast of pathological changes between HBc-E1/2 group and adjuvant group. Mice born to HBc-E1/2 or adjuvant immunized female mice and challenged with pSVA-MP4 or CA16-190 were sacrificed, and the tissues were collected as described in the Materials and Methods. Representative sections analyzed by immunohistochemistry (IHC) or hematoxylin and eosin (HE) staining are shown.
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f3: In vivo cross-protection of HBc-E1/2 to EV71 and CA16.(A) Groups of one-day old BALB/c mice born to female mice immunized with HBc-E1/2, HBc-E1, HBc-E2 or adjuvant with an immunization dose of 100 μg were challenged with pSVA-MP4 or CA16-190. The mortality were monitored and recorded daily for 20 days. The representative results of two independent experiments are shown. (B) Contrast of pathological changes between HBc-E1/2 group and adjuvant group. Mice born to HBc-E1/2 or adjuvant immunized female mice and challenged with pSVA-MP4 or CA16-190 were sacrificed, and the tissues were collected as described in the Materials and Methods. Representative sections analyzed by immunohistochemistry (IHC) or hematoxylin and eosin (HE) staining are shown.

Mentions: Although immunization with the HBc-E1/2 could induce neutralizing antibodies against EV71 and CA16 in adult mice, it is not clear whether materal antibody could protect the neonatal mice from EV71 or CA16 induced illness and death. After the third injection, mice immunized with different dose of HBc-E1/2, HBc-E1, HBc-E2 or adjuvant were allowed to mate. The EV71 mouse-adapted virus pSVA-MP4 at a dose of 107 TCID50 or the CA16 virus 190 at a dose of 105 TCID50 was inoculated i.p. or i.c. to the 1-day-old mice born to the immunized mice, respectively. In the EV71 challenge test, the neonatal mice in the adjuvant group started to show illness at 4 dpi and all died within 11 dpi. One-day-old mice born to dams immunized with HBc-E2 all survived (***P < 0.0001) and were all healthy (Fig. 3A).


A Broadly Cross-protective Vaccine Presenting the Neighboring Epitopes within the VP1 GH Loop and VP2 EF Loop of Enterovirus 71.

Xu L, He D, Yang L, Li Z, Ye X, Yu H, zhao H, Li S, Yuan L, Qian H, Que Y, Shih JW, Zhu H, Li Y, Cheng T, Xia N - Sci Rep (2015)

In vivo cross-protection of HBc-E1/2 to EV71 and CA16.(A) Groups of one-day old BALB/c mice born to female mice immunized with HBc-E1/2, HBc-E1, HBc-E2 or adjuvant with an immunization dose of 100 μg were challenged with pSVA-MP4 or CA16-190. The mortality were monitored and recorded daily for 20 days. The representative results of two independent experiments are shown. (B) Contrast of pathological changes between HBc-E1/2 group and adjuvant group. Mice born to HBc-E1/2 or adjuvant immunized female mice and challenged with pSVA-MP4 or CA16-190 were sacrificed, and the tissues were collected as described in the Materials and Methods. Representative sections analyzed by immunohistochemistry (IHC) or hematoxylin and eosin (HE) staining are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4525384&req=5

f3: In vivo cross-protection of HBc-E1/2 to EV71 and CA16.(A) Groups of one-day old BALB/c mice born to female mice immunized with HBc-E1/2, HBc-E1, HBc-E2 or adjuvant with an immunization dose of 100 μg were challenged with pSVA-MP4 or CA16-190. The mortality were monitored and recorded daily for 20 days. The representative results of two independent experiments are shown. (B) Contrast of pathological changes between HBc-E1/2 group and adjuvant group. Mice born to HBc-E1/2 or adjuvant immunized female mice and challenged with pSVA-MP4 or CA16-190 were sacrificed, and the tissues were collected as described in the Materials and Methods. Representative sections analyzed by immunohistochemistry (IHC) or hematoxylin and eosin (HE) staining are shown.
Mentions: Although immunization with the HBc-E1/2 could induce neutralizing antibodies against EV71 and CA16 in adult mice, it is not clear whether materal antibody could protect the neonatal mice from EV71 or CA16 induced illness and death. After the third injection, mice immunized with different dose of HBc-E1/2, HBc-E1, HBc-E2 or adjuvant were allowed to mate. The EV71 mouse-adapted virus pSVA-MP4 at a dose of 107 TCID50 or the CA16 virus 190 at a dose of 105 TCID50 was inoculated i.p. or i.c. to the 1-day-old mice born to the immunized mice, respectively. In the EV71 challenge test, the neonatal mice in the adjuvant group started to show illness at 4 dpi and all died within 11 dpi. One-day-old mice born to dams immunized with HBc-E2 all survived (***P < 0.0001) and were all healthy (Fig. 3A).

Bottom Line: We demonstrate that anti-VP2 (aa141-155) sera bound authentic CA16 viral particles, whereas anti-VP1 (aa208-222) sera could not.Moreover, the anti-VP2 (aa141-155) antibodies inhibited the binding of human serum to virions, which demonstrated that the VP2 epitope is immunodominant between EV71 and CA16.These results illustrated that the chimeric VLP HBc-E1/2 is a promising candidate for a broad-spectrum HFMD vaccine, and also reveals mechanisms of protection by the neighboring linear epitopes of the VP1 GH and VP2 EF loops.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen 361102, PR China.

ABSTRACT
Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major etiological agents of hand, foot and mouth disease (HFMD) and are often associated with neurological complications. Currently, several vaccine types are being developed for EV71 and CA16. In this study, we constructed a bivalent chimeric virus-like particle (VLP) presenting the VP1 (aa208-222) and VP2 (aa141-155) epitopes of EV71 using hepatitis B virus core protein (HBc) as a carrier, designated HBc-E1/2. Immunization with the chimeric VLPs HBc-E1/2 induced higher IgG titers and neutralization titers against EV71 and CA16 in vitro than immunization with only one epitope incorporated into HBc. Importantly, passive immunization with the recombinant HBc-E2 particles protected neonatal mice against lethal EV71 and CA16 infections. We demonstrate that anti-VP2 (aa141-155) sera bound authentic CA16 viral particles, whereas anti-VP1 (aa208-222) sera could not. Moreover, the anti-VP2 (aa141-155) antibodies inhibited the binding of human serum to virions, which demonstrated that the VP2 epitope is immunodominant between EV71 and CA16. These results illustrated that the chimeric VLP HBc-E1/2 is a promising candidate for a broad-spectrum HFMD vaccine, and also reveals mechanisms of protection by the neighboring linear epitopes of the VP1 GH and VP2 EF loops.

No MeSH data available.


Related in: MedlinePlus