Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine was developed in the 1960s. However, this vaccine does not prevent infection in RSV-na€ ıve recipients and has the paradoxical effect of increasing the severity of RSV illness following natural infection, which has been a major obstacle to developing RSV vaccines. Several experimental animal models for determining the cause of the severe symptoms in FI-RSV recipients have been developed. In the present study, cotton rats immunized with FI-RSV were challenged with RSV and histopathological findings and recovery of infectious virus were studied. Copy numbers of mRNA of Th1 and Th2 cytokines were measured in lung tissues to gain better understanding of their immune responses. Infiltration of inflammatory cells and prominent interstitial pneumonitis were observed in the FI-RSV group, as was induction of mRNA of Th2 cytokines such as IL-4, IL-10, IL-13 and RANTES. Rats immunized with recombinant measles virus expressing the RSV F protein (MVAIK/RSV/F) and those treated with anti-RSV mAb (palivizumab) showed very mild interstitial pneumonitis. Amounts of mRNA of IL-1b, IFN-g and IL-4 were higher in the MVAIK/RSV/F group. Administration of palivizumab before RSV challenge decreased the severity of interstitial pneumonitis in the FI-RSV group. FI-RSV induced skewed Th2 responses, resulting in severe inflammatory responses.