Immunogenicity of influenza tetravalent inactivated subunit adjuvant vaccine in healthy and in patients with primary immune deficiency

National Research Center – Institute of Immunology, Moscow, Russia, The 8th International Medical Congress for Students and Young Doctors, September 24-26, 2020Introduction. Vaccination is the most effective means of influenza prevention. The current epidemiological influenza situation in the world indicates that trivalent vaccines are not able to protect the population from all circulating strains of type B influenza virus, that necessitates the improvement and expansion of the composition of the vaccines.Aim of the study. To evaluate the immunogenicity of influenza tetravalent inactivated subunit adjuvant vaccine in healthy adults and in patients with common variable immune deficiency. Materials and methods. In a single-center, open-label, non-randomized, prospective, cohort, controlled study before the flu season 2018-2019 were involved 32 healthy volunteers aged 18- 50 years and the comparison group which consisted of 6 patients with a confirmed diagnosis of common variable immune deficiency (CVID). All patients received 1 dose (0,5 ml) of the first Russian quadrivalent inactivated subunit vaccine (IIV4) with a decreased amount hemagglutinin protein (20 mkg of influenza H-antigens instead of 60 mkg in standart nonadjuvant IIV4 in the world) due to the use of azoximer bromide (500 mkg per dose). The antibody levels against the influenza type A viruses (H1N1 and H3N2) and two type B viral cell lines (B/Yamagata and B/Victoria) were evaluated using a hemagglutination inhibition reaction. The seroprotection, seroconversion, geometric mean titer rates, CD-subpopulations (CD3+, CD4+, CD8+, CD16,56+, CD19+, CD21+) and expression of toll-like receptors 3, 8, 9 were analized. Results. Adjuvant IIV4 in healthy adults elicited comparable immune response for matched 4 influenza strains with explored non-adjuvant IIV4 in the world. Patients with common variable immune deficiency failed to form a protective humoral immune response to adjuvant IIV4 although CD-subpopulations and expression of toll-like receptors 3, 8, 9 were similar to healthy controls that may indirectly indicate the possibility of the formation of cellular immunity in response to vaccination in these patients. Conclusions. The use of adjuvant IIV4 allows to form protection against 2 circulating influenza B lineages without reduction of the immunogenicity in relation to influenza strains type A. To evaluate the effectiveness of the influenza vaccine in patients with PID it is necessary to study other mechanisms of the development of a postvaccinal immune response

The Efficacy of Immunoadjuvant-Containing Influenza Vaccines in Pregnancy

The aim of the work was to determine the clinical safety and immunogenicity of immunoadjuvant vaccines against influenza (MonoGripol Plus and Grippol® Plus) in 182 pregnant women in the II and III trimesters of gestation, and further assessment of fetal conditions and infants of the first 6 months of life. Results: It was shown that immunoadjuvant vaccines do not have a negative effect on the physiological course of pregnancy and the functional state of the fetoplacental complex. In the early postpartum period, the rates of physical and neuro-psychological development and the nature of feeding of children did not differ from the control group. In pregnant women vaccinated with Grippol® plus, the levels of seroprotection to strains of A/H1N1/v are 82.0%, A/H3N2/—88.0%, B—88.3% that measure the CPMP criteria and last more than a year . After birth, transplacental antibodies in children in protective values were observed in 52.3–68.9% of cases, did not differ from the control group, and disappear after 6 months. Respiratory infections during the first 6 months of life of infants born from mothers vaccinated against influenza registered in 1.8 times less frequently

Immunogenicity and safety of subunit influenza vaccines in pregnant women

Pregnancy is a condition of modulated immune suppression, so this group of patients has increased risk of infectious diseases. Trivalent subunit vaccines, unadjusted Agrippal S1 (group I) and immunoadjuvant Grippol Plus (group II), containing 5 μg of actual influenza virus strains, were administered respectively to 37 and 42 women in the second and third trimester of physiological pregnancy. The administration of subunit influenza vaccines was accompanied by the development of local reactions in no more than 10% of patients, compared with 4.9% of the 41 pregnant women in the placebo group (group III). Systemic reactions were of a general somatic nature, did not differ between vaccinated and placebo groups, and were not associated with vaccination. Physiological births in groups I, II and III were 94.6%, 92.9% and 85.4%, respectively, and the birth rates of children without pathologies were 91.9%, 90.5% and 80.5%, respectively, and were comparable between groups. Vaccination stimulated the production of protective antibodies against influenza virus strains in 64.8–94.5% of patients after immunisation with an unadjusted vaccine and in 72.5–90.0% of patients after the administration of an immunoadjuvant vaccine. After 9 months, antibody levels were recorded in 51.3–72.9% in group I and 54.2–74.2% in group II. Immunisation against influenza in pregnant women provided a high level of seroprotection and seroconversion. Nevertheless, the level of seroprotection against the influenza strain A(H3N2, Victoria) was slightly lower in the group immunised with an unadjusted vaccine compared to those vaccinated with the immunoadjuvant vaccine

Prospective randomized open-label comparative study of immunogenicity after subunit and polymeric subunit influenza vaccines administration among mothers and infants

Pregnant women are risk group for influenza infection. Results of new subunit vaccines application have not been studied enough. Prospective, randomized, open-label comparative study of subunit (Agrippal) and polymeric subunit (Grippol plus) vaccines. 42 pairs of mothers-infants were participated in the study. Protective antibodies (≥ 1:40) to different influenza strains were registered on day 1 after the birth on the same level as 53% of cases in pairs mothers-infants after immune adjuvant polymeric subunit and subunit vaccines administration. There were the same level of protective antibodies (AB) among mothers after 3 month, but transplacental antibodies decreased among infants and registered in the 13–22% cases of Grippol plus group and 31–43% cases in Agrippal S1 group. AB titre to influenza virus A/H1N1/pdm09 and A/H3N2/in pairs mothers-infants were the same in both groups in first days after birth, but AB levels to B strain were lower among infants without regard to vaccine. There is no difference in AB titres among infants of both groups at 3 month of age, but their levels were twice lower versus initial data. An immune adjuvant polymeric subunit as well as subunit vaccines application in pregnant women forms protective AB in pairs mothers-infants

Immunogenicity and Safety of the Quadrivalent Adjuvant Subunit Influenza Vaccine in Seropositive and Seronegative Healthy People and Patients with Common Variable Immunodeficiency

Background. Influenza prophylaxis with the use of quadrivalent vaccines (QIV) is increasingly being introduced into healthcare practice. Methods. In total, 32 healthy adults and 6 patients with common variable immunodeficiency (CVID) received adjuvant QIV during 2018–2019 influenza season. Depending on initial antibody titers, healthy volunteers were divided into seronegative (≤1:20) and seropositive (≥1:40). To evaluate immunogenicity hemagglutination inhibition assay was used. Results. All participants completed the study without developing serious post-vaccination reactions. Analysis of antibody titer 3 weeks after immunization in healthy participants showed that seroprotection, seroconversion levels, GMR and GMT for strains A/H1N1, A/H3N2 and B/Colorado, B/Phuket among initially seronegative and seropositive participants meet the criterion of CHMP effectiveness. CVID patients showed increase in post-vaccination antibody titer without reaching conditionally protective antibody levels. Conclusion. Adjuvant QIV promotes formation of specific immunity to vaccine strains, regardless of antibodies’ presence or absence before. In CVID patients search of new regimens should be continued

Secretory IgA and course of COVID-19 in patients receiving a bacteria-based immunostimulant agent in addition to background therapy

Abstract Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA) might contribute to the activation of the immune response mechanisms. To assess the levels of sIgA produced by epithelial cells in the nasal and pharyngeal mucosa and those measured in salivary gland secretions and to study the course of COVID-19 following the combined scheme of intranasal and subcutaneous administration of a bacteria-based immunostimulant agent. This study included 69 patients, aged between 18 and 60, who had moderate COVID-19 infection. They were divided into two groups: Group 1 (control group) included 39 patients who received only background therapy, and Group 2 was made up of 30 patients who received background therapy in combination with the Immunovac VP4 vaccine, a bacteria-based immunostimulant agent, which was given for 11 days starting from the day of admission to hospital. The levels of sIgA were measured by ELISA in epithelial, nasal and pharyngeal swabs, and salivary gland secretions at baseline and on days 14 and 30. The combined scheme of intranasal and subcutaneous administration of the Immunovac VP4 vaccine in the complex therapy of patients with COVID-19 is accompanied by increased synthesis of sIgA in nasal and pharyngeal swabs, more intense decrease in the level of C-reactive protein (CRP) and reduction in the duration of fever and length of hospitalization compared to the control group. Prescribing a immunostimulant agent containing bacterial ligands in complex therapy for COVID-19 patients helps to enhance mucosal immunity and improves the course of the disease