Simultaneous infection with gammaherpes and influenza viruses enhances the host immune defense.

We have studied the impact of simultaneous infection of mice with murine gammaherpesvirus (MHV) and influenza A virus (IAV) on the immune response and pathogenesis of both infections. After a persistent MHV-68 herpesviral infection had been established, the same mice were super-infected with IAV. Individual parameters of MHV infection (viral DNA detection in organs and blood) and numbers of leukocytes in lungs and spleens were determined. With regard to the assumed reactivation of MHV-68 (mainly in lungs, spleen, thymus and peritoneal exudate cells) we focused our attention on the detection of transcripts, typical either for lytic infection (ORF50) and/or for latency (ORF73). Herpesviral DNA was detected in above mentioned organs in several intervals during the acute phase of IAV co-infection, but the expression of monitored transcripts was lower, i.e. it has decreased. Though the reason for such limited expression during acute influenza superinfection remains unclear, it is unambiguous that lower MHV-68 expression was detected in lungs and peritoneal exudate cells (PECs) from 3rd to 10th day after co-infection with IAV. Furthermore, our study showed that the ongoing gammaherpesvirus latency in co-infected mice affected the number of cytotoxic T-lymphocytes and neutrophils during the acute IAV infection and lowered their deviations from that of non-infected mice. Therefore, we suppose that co-infection with herpes and influenza viruses could be mutually beneficial for the host by promoting its defense against both viruses.

Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses.

In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.

Two distinct regions of HA2 glycopolypeptide of influenza virus hemagglutinin elicit cross-protective immunity against influenza.

UNLABELLED: Currently, a new trend in development of vaccines against influenza with broader spectrum of efficacy is focused on conserved antigens of influenza virus. The HA2 glycopolypeptide (HA2 gp) is one of conserved antigens, potentially suitable as immunogens inducing cross-protection against influenza. We selected two distinct domains of HA2 gp originating from influenza A virus (IAV) of H3 subtype for induction of antiviral immune response: the ectodomain (EHA2) comprising aa 23-185 and the fusion peptide (FP) comprising N-terminal aa 1-38. BALB/c mice were immunized with three doses of EHA2 and FP, respectively, and subsequently challenged with 2 LD50 of IAV of homologous (H3) or heterologous (H7) HA subtype. Both peptides induced significant antibody response and protected mice against the lethal infection. The most efficient protection was achieved with EHA2 against homologous virus. KEYWORDS: influenza A virus; cross-protection; HA2 glycopolypeptide; HA2 ectodomain; fusion peptide; mice; vaccine.

Trends in development of the influenza vaccine with broader cross-protection.

Influenza A viruses cause in humans acute respiratory infections, which spread yearly in the form of epidemics or pandemics. A high variability and broad host specificity of influenza A viruses are the main reasons of repeated influenza infections. Therefore, no effective prevention against influenza is available today. The main problem of insufficient protection efficacy is that virus-neutralizing antibodies induced by current vaccines are closely strain-specific and the vaccines need to be updated each year. Therefore, various novel approaches to vaccine preparation have been developed with the aim to widen the spectrum of their efficacy. These approaches comprise using new adjuvants as components of the inactivated vaccines, new techniques of live attenuated vaccine preparation (reverse genetics), and new vaccine design focused on the conserved antigens of influenza A viruses inducing protective immunity not only against the influenza viruses antigenically similar (homologous) to vaccine strains, but also against heterologous viruses, even of different subtypes. In this review examples of new approaches to the induction of intersubtype immunity against influenza and their utilization in vaccine preparation are described.