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Universal vaccine against respiratory syncytial virus A and B subtypes

View Article: PubMed Central - PubMed

ABSTRACT

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131–230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.

No MeSH data available.


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Pulmonary cell infiltration in GcfAB-immune mice following RSV A subtype challenge.After two rounds of GcfAB vaccine administration, the GcfAB-immune groups were challenged with RSV A2 and then sacrificed at 5 and 7 days post-challenge. (A) BAL cells were harvested and then stained with anti-CD45, Siglec-F, Gr-1, and CD11c antibodies and analyzed by flow cytometry. (B and C) Eosinophils and neutrophils among CD45+-gated cells were quantitated. All data represented in mean ± SD (n = 4/group). Significant differences from the PBS group are marked with asterisks (*). p < 0.05.
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pone.0175384.g007: Pulmonary cell infiltration in GcfAB-immune mice following RSV A subtype challenge.After two rounds of GcfAB vaccine administration, the GcfAB-immune groups were challenged with RSV A2 and then sacrificed at 5 and 7 days post-challenge. (A) BAL cells were harvested and then stained with anti-CD45, Siglec-F, Gr-1, and CD11c antibodies and analyzed by flow cytometry. (B and C) Eosinophils and neutrophils among CD45+-gated cells were quantitated. All data represented in mean ± SD (n = 4/group). Significant differences from the PBS group are marked with asterisks (*). p < 0.05.

Mentions: According to previous reports, RSV G-expressing vaccine candidates, such as vvG or subunit vaccines, consisting in part of the RSV G protein, showed excessive pulmonary eosinophilia following live RSV infection [14, 15, 18]. To investigate whether GcfAB immunization leads to pulmonary cell infiltration, GcfAB-immune mice were challenged with either RSV A2 (Fig 7) or RSV B (KR/B/10-12) (Fig 8). Five and 7 days post-challenge, we measured the percentages of both eosinophils and neutrophils in bronchoalveolar lavage (BAL) cells by flow cytometry (Figs 7A and 8A). After RSV A subtype challenge, the GcfAB SL group exhibited greater recruitment of eosinophils than did the GcfAB IN group, and the number of eosinophils was increased at 7 days compared to 5 days (Fig 7B). The vvG immune group (positive control) showed a significantly increased number and percentage of eosinophils, while the PBS group did not exhibit any detectable eosinophil recruitment (Fig 7B). The percent of neutrophils was significantly reduced in the GcfAB-immune groups compared with the PBS group at 7 days (Fig 7C), but both the percentage and number of neutrophils were not significantly different between the PBS and GcfAB-immune groups (p > 0.05) at 5 days (Fig 7C).


Universal vaccine against respiratory syncytial virus A and B subtypes
Pulmonary cell infiltration in GcfAB-immune mice following RSV A subtype challenge.After two rounds of GcfAB vaccine administration, the GcfAB-immune groups were challenged with RSV A2 and then sacrificed at 5 and 7 days post-challenge. (A) BAL cells were harvested and then stained with anti-CD45, Siglec-F, Gr-1, and CD11c antibodies and analyzed by flow cytometry. (B and C) Eosinophils and neutrophils among CD45+-gated cells were quantitated. All data represented in mean ± SD (n = 4/group). Significant differences from the PBS group are marked with asterisks (*). p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383302&req=5

pone.0175384.g007: Pulmonary cell infiltration in GcfAB-immune mice following RSV A subtype challenge.After two rounds of GcfAB vaccine administration, the GcfAB-immune groups were challenged with RSV A2 and then sacrificed at 5 and 7 days post-challenge. (A) BAL cells were harvested and then stained with anti-CD45, Siglec-F, Gr-1, and CD11c antibodies and analyzed by flow cytometry. (B and C) Eosinophils and neutrophils among CD45+-gated cells were quantitated. All data represented in mean ± SD (n = 4/group). Significant differences from the PBS group are marked with asterisks (*). p < 0.05.
Mentions: According to previous reports, RSV G-expressing vaccine candidates, such as vvG or subunit vaccines, consisting in part of the RSV G protein, showed excessive pulmonary eosinophilia following live RSV infection [14, 15, 18]. To investigate whether GcfAB immunization leads to pulmonary cell infiltration, GcfAB-immune mice were challenged with either RSV A2 (Fig 7) or RSV B (KR/B/10-12) (Fig 8). Five and 7 days post-challenge, we measured the percentages of both eosinophils and neutrophils in bronchoalveolar lavage (BAL) cells by flow cytometry (Figs 7A and 8A). After RSV A subtype challenge, the GcfAB SL group exhibited greater recruitment of eosinophils than did the GcfAB IN group, and the number of eosinophils was increased at 7 days compared to 5 days (Fig 7B). The vvG immune group (positive control) showed a significantly increased number and percentage of eosinophils, while the PBS group did not exhibit any detectable eosinophil recruitment (Fig 7B). The percent of neutrophils was significantly reduced in the GcfAB-immune groups compared with the PBS group at 7 days (Fig 7C), but both the percentage and number of neutrophils were not significantly different between the PBS and GcfAB-immune groups (p > 0.05) at 5 days (Fig 7C).

View Article: PubMed Central - PubMed

ABSTRACT

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131&ndash;230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.

No MeSH data available.


Related in: MedlinePlus