Protection by humoral elements independent of virus neutralization activity against an influenza virus challenge.

To investigate the protective efficacy of a seasonal trivalent inactivated whole virion influenza vaccine (TIV) adjuvanted with aluminum phosphate (Fluval AB, referred to here as TIV+Al), we immunized mice with the TIV+Al, and as controls, with TIV, TIV+Al combined with Freund adjuvant (TIV+Al+F), inactivated A/PR/8/34(H1N1) (PR8) strain or PBS, and challenged them with a lethal dose of a mouse-adapted PR8 virus. Serum pools from immunized mice were passively transferred to recipient mice that were then challenged similarly. All actively immunized mice survived the challenge. Of recipient mice receiving serum from mice actively immunized with TIV, TIV+Al or TIV+Al+F, 20%, 80%, and 100% survived, respectively. Rates of mortality and morbidity of recipient mice were inversely proportional to the hemagglutination inhibition (HI) antibody level to the vaccine virus in the absence of detectable PR8-specific HI, neuraminidase inhibition (NI) and virus neutralization (VN) antibodies. No cross-reactivity was observed between vaccine and PR8 strains in in vitro HI, NI or VN assays. In splenocytes from TIV+Al-immunized mice production of IFN-γ or granzyme-B protein and mRNA expression increased (p<0.05). Thus, antibodies play a major role in the protection against a mismatched challenge infection independent of HI, NI and VN activity, but cellular immune responses may contribute to full protection in actively immunized mice.

Protection of Chinese painted quails (Coturnix chinensis) against a highly pathogenic H5N1 avian influenza virus strain after vaccination.

Chinese painted quails immunized with a single dose (6 µg HA) of inactivated H5N1 (clade 1) influenza vaccine NIBRG-14 and challenged with 100 LD50 of the heterologous A/Swan/Nagybaracska/01/06(H5N1) (clade 2.2) strain were protected, whereas unvaccinated quails died after challenge. No viral antigens or RNA were detected in cloacal swabs from immunized animals. Sera obtained post-immunization gave low titres in serological assays against the vaccine and the challenge viruses. Our results demonstrate the protective efficacy of the NIBRG-14 strain against the challenge virus and the usefulness of these small birds in protection studies of influenza vaccines.

[Importance of the case of coronavirus-associated severe acute respiratory syndrome detected in Hungary in 2005]. / Miért aktuális 2013-ban a súlyos akut respirációs szindrómát okozó coronavírus-fertozés 2005-ben Magyarországon igazolt esete?

Ten years have elapsed since the severe acute respiratory syndrome outbreak, which resulted in more than 8000 cases worldwide with more than 700 deaths. Recently, a new coronavirus, the Middle East Respiratory Syndrome Coronavirus emerged, causing serious respiratory cases and death. By the end of August 2013, 108 cases including 50 deaths were reported. The authors discuss a coronavirus-associated severe acute respiratory syndrome, which was detected in Hungary in 2005 and highlight its significance in 2013. In 2005 the patient was hospitalized and all relevant clinical and microbiological tests were performed. Based on the IgG antibody positivity of the serum samples, the patient was diagnosed as having severe acute respiratory syndrome coronavirus infection in the past. The time and source of the infection remained unknown. The condition of the patient improved and he was discharged from the hospital. The case raises the possibility of infections in Hungary imported from remote areas of the world and the importance of thorough examination of patients with severe respiratory syndrome with unknown etiology.

Asymptomatic and Mild SARS-CoV-2 Infections in a Hungarian Outpatient Cohort in the First Year of the COVID-19 Pandemic.

We aimed to estimate the proportion of the population infected with SARS-CoV-2 in the first year of the pandemic. The study population consisted of outpatient adults with mild or no COVID-19 symptoms and was divided into subpopulations with different levels of exposure. Among the subpopulation without known previous COVID-19 contacts, 4143 patients were investigated. Of the subpopulation with known COVID-19 contacts, 594 patients were investigated. IgG- and IgA-seroprevalence and RT-PCR positivity were determined in context with COVID-19 symptoms. Our results suggested no significant age-related differences between participants for IgG positivity but indicated that COVID-19 symptoms occurred most frequently in people aged between 20 and 29 years. Depending on the study population, 23.4-74.0% PCR-positive people (who were symptomless SARS-CoV-2 carriers at the time of the investigation) were identified. It was also observed that 72.7% of the patients remained seronegative for 30 days or more after their first PCR-positive results. This study hoped to contribute to the scientific understanding of the significance of asymptomatic and mild infections in the long persistence of the pandemic.

High-level cellular and humoral immune responses in Guinea pigs immunized intradermally with a heat-inactivated varicella-zoster virus vaccine.

The threat of varicella and herpes zoster in immunocompromised individuals necessitates the development of a safe and effective varicella-zoster virus (VZV) vaccine. The immune responses of guinea pigs to the intradermal (i.d.) or subcutaneous (s.c.) administration of a heat-inactivated or live VZV vaccine were investigated. Relative to nonimmunized animals, a single 399-PFU dose of vaccine induced nonsignificant increases in gamma interferon (IFN-γ), granzyme B, and perforin mRNA expression in the splenocytes of all groups, while two i.d. administrations of the inactivated vaccine increased IFN-γ mRNA expression significantly (P < 0.005). A single 1,995-PFU dose significantly increased the expression of IFN-γ mRNA in the groups receiving the vaccine either i.d. (P < 0.005) or s.c. (P < 0.05), that of granzyme B mRNA in the groups immunized i.d. with the inactivated (P < 0.005) or live (P < 0.005) vaccine, and that of perforin mRNA in the animals that received the inactivated vaccine i.d. (P < 0.005). Importantly, increases in the expression of IFN-γ (P = 0.025), granzyme B (P = 0.004), and perforin (P > 0.05) mRNAs were observed in the animals immunized i.d. with 1,995 PFU of inactivated vaccine relative to those immunized s.c. with the same dose. The proportion of animals expressing IFN-γ mRNA mirrored the proportion expressing IFN-γ protein (correlation coefficient of 0.88). VZV glycoprotein-specific and virus-neutralizing antibodies were produced with no significant intergroup differences. A booster i.d. administration of the 399-PFU dose of heat-inactivated vaccine enhanced the antibody responses. These results demonstrate that i.d. administration of an inactivated VZV vaccine can be an efficient mode of immunization against VZV.

Fast vaccine design and development based on correlates of protection (COPs).

New and reemerging infectious diseases call for innovative and efficient control strategies of which fast vaccine design and development represent an important element. In emergency situations, when time is limited, identification and use of correlates of protection (COPs) may play a key role as a strategic tool for accelerated vaccine design, testing, and licensure. We propose that general rules for COP-based vaccine design can be extracted from the existing knowledge of protective immune responses against a large spectrum of relevant viral and bacterial pathogens. Herein, we focus on the applicability of this approach by reviewing the established and up-coming COPs for influenza in the context of traditional and a wide array of new vaccine concepts. The lessons learnt from this field may be applied more generally to COP-based accelerated vaccine design for emerging infections.

Varicella-zoster virus vaccine, successes and difficulties.

Despite intensive efforts in recent decades to develop preventive or therapeutic vaccines against diseases caused by herpes simplex virus (HSV), or varicella-zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes viruses,a safe and efficient vaccine has been approved for commercial development only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It consists of amixture of at least 13 subpopulations of viruses, all with deletions, insertions or mutations in the genome; the most common mutations are observed in the open reading frame 62 (ORF62). Experience over more than 30 years in Japan, the USA and other countries where VZV vaccination is provided has demonstrated that the vaccine is safe and the effectiveness of two doses compared to unvaccinated children is 98-99%. When administered in a higher dose to stimulate the declining cell-mediated immunity, the same vaccine has been shown to reduce the incidence and severity of herpes zoster in immunocompetent individuals older than 60 years. Vaccination of immuno-compromised subjects with this VZV vaccine is problematic and various strategies need to be explored. Differences in the pathomechanisms of infection, latency and immune evasion of VZV and HSV, together with host genetic factors, may explain the availability of the successful VZV vaccine and the failures of the past HSV vaccine candidates.