Impaired serum antibody response to inactivated influenza A and B vaccine in cancer patients.

The serum antibody response to vaccination with bivalent inactivated influenza vaccine containing A/Port Chalmers/1/73 (H3N2) and B/Hong Kong/5/72 antigens was assessed in 44 patients with cancer and in 27 healthy control subjects. A fourfold or greater increase in antibody titre after vaccination occurred in 16 of the 44 cancer patients and 25 of the 27 controls for the A antigen, and in 14 of the 44 cancer patients and 20 of the 27 controls for the B antigen. Patients with lymphoma, who tended to have hypogammaglobulinemia, responded less well than did patients with solid tumours. Among the latter the failure to show a fourfold or greater increase in antibody titre correlated with a poorer 18-month survival.     

The antibody response of seronegative infants to inactivated poliovirus vaccine of enhanced potency

The immunogenic efficacy of inactivated poliovirus vaccine of enhanced potency (IPV-E), containing 40, 8 and 32 D-antigen units of types 1, 2 and 3, respectively, was evaluated in tritypic seronegative infants. Eighty infants aged six to 45 weeks, with no antibody detectable at a 1 : 4 dilution, were given two doses of a quadruple vaccine containing diphtheria-pertussis-tetanus (DPT) vaccine and IPV-E at intervals of four weeks (37 infants, group 1) or eight weeks (43 infants, group 2) between doses. All infants of group 2 responded with antibody to the three types of polioviruses. In group 1, all responded to types 1 and 3 antigens but only 36 responded to type 2. Antibody titres were higher in infants immunized at eight week than at four week intervals. Thus, two doses of IPV-E, especially when given eight weeks apart, are sufficient for primary immunization against poliomyelitis. If DPT vaccine of enhanced potency is combined with IPV-E, two doses of such a quadruple vaccine may be sufficient for primary immunization against four diseases; this possibility deserves evaluation.     

Toxicities of influenza vaccine: peripheral leukocytic response to live and inactivated influenza viruses in mice.

Intraperitoneal or intravenous inoculation of live or inactivated influenza virus induced two characteristic responses of the peripheral leukocytes in mice, an early appearing leukopenic response and late appearing lymphopenia. The former response usually developed and subsided within several hours, though the change in leukocyte population was fairly complicated depending upon the activity of the inoculated material, while the latter began several hours after inoculation and reached its minimum level in 10 to 20 hr. The agent responsible for the former may be virus pyrogen, while the latter seems to be caused by some substance(s) other than that. The early appearing leukopenic response was similar to that due to bacterial endotoxin in respect to the characteristic pattern of the change in peripheral leukocyte population, though it was relatively easy to distinguish one from the other by the length of the latent period and by the heat stability of the causative agent. Live or inactivated influenza virus causing the early appearing leukopenic response was found also to have the mouse body weight-decreasing toxicity. The significance of these findings in the laboratory control test of influenza vaccine for untoward reactions often observed in human inoculated with some inactivated influenza vaccines was discussed. The possible roles of the two agents, virus pyrogen and endotoxin, in the febrile response were mentioned.     

Evaluation of determinants of the serological response to the quadrivalent split‐inactivated influenza vaccine

The seasonal influenza vaccine is only effective in half of the vaccinated population. To identify determinants of vaccine efficacy, we used data from > 1,300 vaccination events to predict the response to vaccination measured as seroconversion as well as hemagglutination inhibition (HAI) titer levels one year after. We evaluated the predictive capabilities of age, body mass index (BMI), sex, race, comorbidities, vaccination history, and baseline HAI titers, as well as vaccination month and vaccine dose in multiple linear regression models. The models predicted the categorical response for > 75% of the cases in all subsets with one exception. Prior vaccination, baseline titer level, and age were the major determinants of seroconversion, all of which had negative effects. Further, we identified a gender effect in older participants and an effect of vaccination month. BMI had a surprisingly small effect, likely due to its correlation with age. Comorbidities, vaccine dose, and race had negligible effects. Our models can generate a new seroconversion score that is corrected for the impact of these factors which can facilitate future biomarker identification.     

Specific prophylaxis of influenza with inactivated split vaccine Vaxigrip

Influenza remains a serious health problem, annually causing epidemics embracing up to 10% of the population of the world, and at the periods of pandemics this number may rise 4- to 6-fold. In the overwhelming majority of the countries the prophylaxis of influenza is carried out at present out with the use of inactivated vaccines. One of such vaccines is the highly purified split vaccine Vaxigrip (Aventis-Pasteur, France), permitted for use in Russia since 1992. The article contains the review of the data of literature, as well as the materials provided by the authors, which indicate that the preparation has low reactogenicity (also for children starting from the age of 6 months) and high reactogenic properties, leading to antibody formation at protective levels with respect to all three components of the vaccine. The vaccine has been found to ensure pronounced prophylactic efficacy for 70-90% of vaccinees and a decrease in influenza morbidity even in case of using the preparation a week before the onset of the epidemic. This shows the advantage of Vaxigrip in comparison with other inactivated vaccines.     

From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza

Over the past eight years, cases of human infection with highly pathogenic avian influenza viruses have raised international concern that we could be on the brink of a global influenza pandemic. Many of these human infections have proved fatal and if the viruses had been able to transmit efficiently from person to person, the effects would have been devastating. How can we arm ourselves against this pandemic threat when these viruses are too dangerous to use in conventional vaccine production? Recent technological developments (reverse genetics) have allowed us to manipulate the influenza virus genome so that we can construct safe, high-yielding vaccine strains. However, the transition of reverse-genetic technologies from the research laboratory to the manufacturing environment has presented new challenges for vaccine manufacturers as well as veterinary and public health authorities.     

Protection of inactivated influenza virus vaccine against lethal influenza virus infection in diabetic mice

Influenza virus infection frequently causes complications and some excess mortality in the patients with diabetes. Vaccination is an effective measure to prevent influenza virus infection. In this paper, antibody response and protection against influenza virus infection induced by vaccination were studied in mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized once or twice with inactivated influenza virus vaccine at various dosages. Four weeks after the first immunization or 1 week after the second immunization, the mice were challenged with influenza virus at a lethal dose. The result showed that the antibody responses in diabetic mice were inhibited. Immunization once with high dose or twice with low dose of vaccine provided full protection against lethal influenza virus challenge in diabetic mice, however, in healthy mice, immunization only once with low dose provided a full protection.     

Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus infection in ferrets

The influenza virus H1N1 pandemic of 1918 was one of the worst medical catastrophes in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus [A(H1N1)pdm09], the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV), share cross-reactive antigenic determinants. In this study, we demonstrate that immunization with the 2010-2011 seasonal TIV induces neutralizing antibodies that cross-react with the reconstructed 1918 pandemic virus in ferrets. TIV-immunized ferrets subsequently challenged with the 1918 virus displayed significant reductions in fever, weight loss, and virus shedding compared to these parameters in nonimmune control ferrets. Seasonal TIV was also effective in protecting against the lung infection and severe lung pathology associated with 1918 virus infection. Our data demonstrate that prior immunization with contemporary TIV provides cross-protection against the 1918 virus in ferrets. These findings suggest that exposure to A(H1N1)pdm09 through immunization may provide protection against the reconstructed 1918 virus which, as a select agent, is considered to pose both biosafety and biosecurity threats.     

Influence of multiplicity of immunizations of children with inactivated influenza vaccine on immune response and the effectiveness of protection

The formation of immunity and epidemiological effectiveness of inactivated influenza vaccines in children, regularly immunized against influenza for three years, were evaluated. The study revealed that a year after each immunization the number of children having antibodies in liters regarded as protective decreased 2-2.5 times. At the periods of epidemics morbidity rate among the vaccines dynamically decreased in these years 1.3, 2.0 and 2.8 times. Considering that a year after the second immunization a high immune stratum (60-78%) was retained in the group under study, we propose that annual immunization of the same children be limited by a period of three years, followed by an interval of one year.     

流行性感冒灭活疫苗人体免疫效果及评价

通过对兰州生物制品研究所试生产的流行性感冒灭活疫苗的体试验研究,兰州所流感灭活疫苗接种后,所有接种对象均未见红肿,硬结等局部反应,仅有1例发生在儿童组的低热全身反应（体温37．4℃）,72小时后恢复正常,整体副反应发生率0．274％,肯定了该疫苗的安全性,疫苗接种前后易人群血清血凝抑制（HI）抗体阳转率100％,非易感人群HI抗体几何平均效价（GMT）增长19－60倍,抗体4倍增长率最低为95％,成人组平均值最高（97．67％）,证实该疫苗具有较好的免疫原性。