Attenuated Bordetella pertussis vaccine protects against respiratory syncytial virus disease via an IL-17-dependent mechanism.

Rationale: We attenuated virulent Bordetella pertussis by genetically eliminating or detoxifying three major toxins. This strain, named BPZE1, is being developed as a possible live nasal vaccine for the prevention of whooping cough. It is immunogenic and safe when given intranasally in adult volunteers.

Emerging drugs for respiratory syncytial virus infection.

Although respiratory syncytial virus (RSV) was discovered > 40 years ago, treatment remains largely supportive. There are no safe and effective vaccines or specific treatments other than prophylaxis with passive antibody therapy (palivizumab). However, there are good reasons to think that the scene may soon change.

Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination.

Priming with the major surface glycoprotein G of respiratory syncytial virus (RSV) expressed by recombinant vaccinia leads to strong Th2 responses and lung eosinophilia during viral challenge. We now show that DNA vaccination in BALB/c mice with plasmids encoding G attenuated RSV replication but also enhanced disease with lung eosinophilia and increased IL-4/5 production. However, formulating the DNA with PLG microparticles reduced the severity of disease during RSV challenge without significantly lessening protection against viral replication.

A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines.

Heat, oxidation and exposure to aldehydes create reactive carbonyl groups on proteins, targeting antigens to scavenger receptors. Formaldehyde is widely used in making vaccines, but has been associated with atypical enhanced disease during subsequent infection with paramyxoviruses. We show that carbonyl groups on formaldehyde-treated vaccine antigens boost T helper type 2 (T(H)2) responses and enhance respiratory syncytial virus (RSV) disease in mice, an effect partially reversible by chemical reduction of carbonyl groups.

Protective and disease-enhancing immune responses induced by recombinant modified vaccinia Ankara (MVA) expressing respiratory syncytial virus proteins.

Modified vaccinia Ankara (MVA) recombinants expressing single or multiple RSV surface proteins (F or G) are promising potential vaccines. We studied humoral and cellular responses induced by MVA-F and MVA-G in mice, comparing them to a formalin inactivated RSV preparation (FI-RSV) known to increase disease severity. MVA-F or MVA-G vaccination enhanced weight loss during RSV challenge, but did not show the lung eosinophilia seen after FI-RSV vaccination.

Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis.

A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from the viral transcription anti-terminator protein M2 (M2(82-90)), linked covalently to human beta2-microglobulin (beta2m). Cutaneous gene-gun immunization of BALB/c mice with this construct induced an antigen-specific CD8+ T-cell memory. After intranasal RSV challenge, accelerated CD8+ T-cell responses were observed in pulmonary lymph nodes and virus clearance from the lungs was enhanced.

Vaccines for the prevention of respiratory viral infections: problems and current status.

Acute respiratory virus infections cause the majority of lower respiratory tract illnesses and hospitalisations of infants and the elderly. The emergence of new respiratory viruses and a high probability that influenza will cause further pandemics highlights the necessity for developing better preventative strategies. Although there is a clear and pressing need for vaccines to prevent respiratory syncytial virus, rhinoviruses, coronaviruses, parainfluenza and human metapneumovirus, progress has been extremely slow.

The molecular basis of the antigenic cross-reactivity between measles and cowpea mosaic viruses.

Two nonrelated viruses, cowpea mosaic virus (wtCPMV) and measles virus (MV), were found to induce cross-reactive antibodies. The nature of this cross-reactivity was studied and results are presented here demonstrating that antiserum raised against wtCPMV reacted with peptide from the fusion (F) protein of MV. Furthermore, the F protein of MV was shown to share an identical conformational B cell epitope with the small subunit of CPMV coat protein.

Development of vaccines against common colds.

Respiratory tract viruses are particularly significant causes of illness and death in children and in the elderly. Vaccines offer the possibility of decreasing the severity and complications of viral respiratory disease, but development has been delayed by numerous factors. First, there are more than 200 serologically distinct RNA and DNA virus species and strains which cause an essentially similar spectrum of disease.