Intranasal administration of a live non-pathogenic avian H5N1 influenza virus from a virus library confers protective immunity against H5N1 highly pathogenic avian influenza virus infection in mice: comparison of formulations and administration routes of vaccines.

Outbreaks of highly pathogenic avian influenza viruses (HPAIVs) would cause disasters worldwide. Various strategies against HPAIVs are required to control damage. It is thought that the use of non-pathogenic avian influenza viruses as live vaccines will be effective in an emergency, even though there might be some adverse effects, because small amounts of live vaccines will confer immunity to protect against HPAIV infection. Therefore, live vaccines have the advantage of being able to be distributed worldwide soon after an outbreak. In the present study, we found that intranasal administration of a live H5N1 subtype non-pathogenic virus induced antibody and cytotoxic T lymphocyte responses and protected mice against H5N1 HPAIV infection. In addition, it was found that a small amount (100 PFU) of the live vaccine was as effective as 100 microg (approximately 10(10-11) PFU of virus particles) of the inactivated whole particle vaccine in mice. Consequently, the use of live virus vaccines might be one strategy for preventing pandemics of HPAIVs in an emergency.

Induction of cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza virus infection in mice by inoculation of apathogenic H5N1 influenza virus particles inactivated with formalin.

We investigated whether a vaccine derived from an apathogenic reassortant type A H5N1 influenza strain could induce immune responses in vivo that mediated protection from highly pathogenic avian influenza virus infection in mice. After two subcutaneous immunizations with formalin-inactivated H5N1 whole virus particles (whole particle vaccine), significant killing specific for cells presenting a nucleoprotein peptide from the vaccine strain of the virus was observed. Similar vaccination with viruses treated with ether and formalin, which are commonly used for humans as ether-split vaccines, induced little or no cytotoxic T-cell response. Furthermore, whole particle vaccines of the apathogenic H5N1 strain were more effective than ether-split vaccines at inducing antibody production able to neutralize a highly pathogenic H5N1 strain. Finally, whole particle vaccines of H5N1 protected mice against infection by an H5N1 highly pathogenic avian influenza virus more effectively than did ether-split vaccines. These results suggest that formalin-inactivated virus particles of apathogenic strains are effective for induction of both cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza viruses in vivo, resulting in protection from infection by a highly pathogenic H5N1 virus.

Peptides coupled to the surface of a kind of liposome protect infection of influenza viruses.

In our previous study, OVA conjugated on the surface of a liposome, we termed Oleoyl liposome, which consisted of dioleoyl phosphatidyl choline, dioleoyl phosphatidyl ethanolamine, dioleoyl phosphatidyl glycerol acid and cholesterol in a 4:3:7:2 molar ratio, induced OVA-specific IgG antibody production but not OVA-specific IgE antibody production that is detrimental to the host. Furthermore, OVA(257-264)-Oleoyl liposome elicited CTL responses in the presence of CpG and rejected E.G7 tumors in mice. In this study we tested whether a peptide-Oleoyl liposome conjugates are capable of inducing protection against viral growth. Subcutaneous inoculation of NP(366-374)-Oleoyl liposome with CpG inhibited growth of influenza viruses in lungs of mice. Thus, surface-linked liposomal peptide might serve as an effective vaccine without detrimental effects in the presence of immune potentiators.

Does the lobectomy plus lymph node dissection still remain a standard surgical procedure for patients with cT1N0M0 adenocarcinoma of the lung?

OBJECTIVES: Controversies still exists regarding treatment for cT1N0M0 adenocarcinoma of the lung. The following topics need to be answered: 1) Should all patients undergo lobectomy plus lymph node dissection? and 2) Is there poor-prognostic subgroup that may need adjuvant therapy? METHODS: Between 1990 and 1999, 141 patients with cT1N0M0 adenocarcinoma of the lung underwent lobectomy plus lymph node dissection. Fifteen clinicopathological characteristics of the entire population were investigated with regard to survival. Forty-seven samples, which were possible to reexamine among 68 patients with small adenocarcinoma 2 cm or less in greatest dimension, were assessed according to Noguchi's classification. RESULTS: Nine of fifteen clinicopathological variables were significant in indicating poor prognostic factors in univariate analysis: gender, differentiation, p-T status, p-N status, pm, lymphatic invasion, vascular invasion, pleural invasion, and serum carcinoembryonic antigen (CEA) level. The p-N status and high serum CEA level were independent predictive variables in multivariate analysis. A five-year survival rate for patients with Noguchi's type A and B was 100%. However, six (8.8%) of 68 patients with small adenocarcinoma had lymph node involvement and four patients (5.9%) had pulmonary metastasis. CONCLUSIONS: It is inappropriate and inadequate to omit lobectomy or lymph node dissection only on the basis of tumor size. Therefore, it seems reasonable to conclude that lobectomy plus lymph node dissection still remains as a standard surgical procedure to treat cT1N0M0 adenocarcinoma of the lung. We must continue to search for new deciding factors in order to choose candidates for limited operation among patients with cT1N0M0 adenocarcinoma of the lung.