Abstract
We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.
Highlights
Respiratory syncytial virus (RSV) is a common cause of viral lower respiratory tract infections and causes serious diseases in infants, the elderly, and immunocompromised patients [1]
Infectious recombinant viruses were recovered from recombinant cDNA and virus growth was Infectious viruses were recovered and in virus growth was examined
There was no significant difference in viral growth for the MVAIK, MVAIK/RSA/M2-1, and MVAIK/RSV/NP
Summary
Respiratory syncytial virus (RSV) is a common cause of viral lower respiratory tract infections and causes serious diseases in infants, the elderly, and immunocompromised patients [1]. Of children are infected with RSV in the first year of their lives and nearly 100% by two years of age. RSV causes hospital infections and serious clinical conditions in infants, even though they have high titers of maternal antibodies against RSV [2]. Infants acquire RSV-specific IgG and IgA antibodies and cytotoxic lymphocytes (CTL) after repetitive natural RSV infections [3,4]. The presence of RSV-specific antibodies has been correlated with protection against RSV infection in mice [5]. The formalin-inactivated RSV (FI-RSV) vaccine was developed in the mid-1960s. RSV-naïve infants who received the FI-RSV vaccine developed moderate or severe lower respiratory tract diseases
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