Results of clinical trials of a trivalent vaccine for horses

We have developed a trivalent vaccine made from the SV/69 strain of the Rhinopneumonia virus (RHIV), the bacteria strains of Salmonella abortus equi BN-12 - the causative agent of Salmonella abortion and Streptococcus equi N-34 - the causative agent of the horse strangles. Preclinical laboratory studies of the immunogenicity of the vaccine in linear and outbred mice showed that the preparation protects against experimental infection with the Rhinopneumonia virus by 88.8%, from the causative agents of Salmonella abortion and horse strangles by 100%. There were carried out clinical trials of a trivalent inactivated vaccine with a centrifuge strain Bacillus subtilis TNP-3 as an immunomodulator in order to specifically prevent salmonella abortion, rhinopneumonia and horse strangles. Clinical trials were carried out on horses in the Central regions of Yakutia. The business output of foals was 50.2% in the republic. The business yield in immunized mares was 76,0 % and in unvaccinated mares only 38,0 % in a controlled production trial at the "Uyruye" agricultural production complex. Consequently, immunization of mares with trivalent vaccine increased the reproduction rate by 38,0 %. Results of extensive production tests on 2,568 heads of herd horses confirmed the data of preclinical laboratory studies of immunogenicity in linear and outbred mice. The trivalent vaccine against rhinopneumonia, salmonella abortion and horse strangles stimulates immunobiological reactivity, induces the synthesis of specific antibodies in high titers and increases the business yield of foals from 18,0 to 38,0 %. The vaccine is highly effective and can provide recovery of disadvantaged settlements.

Identification and Characterization of Swine Influenza Virus H1N1 Variants Generated in Vaccinated and Nonvaccinated, Challenged Pigs

Influenza viruses represent a continuous threat to both animal and human health. The 2009 H1N1 A influenza pandemic highlighted the importance of a swine host in the adaptation of influenza viruses to humans. Nowadays, one of the most extended strategies used to control swine influenza viruses (SIVs) is the trivalent vaccine application, whose formulation contains the most frequently circulating SIV subtypes H1N1, H1N2, and H3N2. These vaccines do not provide full protection against the virus, allowing its replication, evolution, and adaptation. To better understand the main mechanisms that shape viral evolution, here, the SIV intra-host diversity was analyzed in samples collected from both vaccinated and nonvaccinated animals challenged with the H1N1 influenza A virus. Twenty-eight whole SIV genomes were obtained by next-generation sequencing, and differences in nucleotide variants between groups were established. Substitutions were allocated along all influenza genetic segments, while the most relevant nonsynonymous substitutions were allocated in the NS1 protein on samples collected from vaccinated animals, suggesting that SIV is continuously evolving despite vaccine application. Moreover, new viral variants were found in both vaccinated and nonvaccinated pigs, showing relevant substitutions in the HA, NA, and NP proteins, which may increase viral fitness under field conditions.

Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants

Rapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particules (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutation. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactivity antibodies.

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.

Efficacy of inactive bivalent and trivalent Streptococcus agalactiae bacteria (biotype 1 & 2) vaccines on tilapia, Oreochromis niloticus

Streptococcosis is a significant fish disease impacting tilapia culture in Indonesia, causing losses estimated up to IDR 15.0 billion annually. This study aims to assess the efficacy of bivalent and trivalent vaccines containing Streptococcus agalactiae bacteria on tilapia. The formula of the bivalent vaccine contains 75% of S01-196-16 and 25% of N14G isolates (v/v). Trivalent vaccine contains 30%, 35%, and 35% of N14G, NP1050, and SG01-16 isolates (v/v), respectively. A challenge test assessed the efficacy of the vaccines, and it was carried out at 30, 90, and 150 days post-vaccination by artificially infection at LD60. Selected bacteria isolate to be appointed in the challenge test are N14G (biotype 2) and S01-196-16 (biotype 1). Relative Percentage of Survival (RPS) was used as the main indicator of vaccine efficacy. The results revealed that the highest RPS of a bivalent vaccine against S. agalactiae (S01-196-16) was achieved at the first challenge (61.84%), and trivalent vaccine against S. agalactiae (N14G) and S. agalactiae (S01-196-16) was achieved at the first challenge (61.53% and 76.20%, respectively). Bivalent and trivalent S. agalactiae bacteria vaccines are promising “tools” to control streptococcosis on tilapia.

Pharmacoeconomic Analysis of Influenza Vaccine Prophylaxis Using Trivalent Vaccine in the Conditions of Healthcare in Kazakhstan

The primary purpose: To assess the clinical and economic effectiveness of influenza vaccination with population coverage of 40% compared with the absence of vaccination and at 10% current coverage in the health system of the Republic of Kazakhstan. The secondary purpose: To carry out an assessment of clinical and economic effectiveness of influenza vaccination in schoolaged children compared with the absence of vaccination Methods. A decision-making model was developed to assess the economic and clinical effectiveness of influenza vaccination in children and adults. Pharmacoeconomic analysis of influenza vaccine prophylaxis with the use of the trivalent vaccine Grippol® plus in the healthcare environment of Kazakhstan. The creation of the model was based on the description of the influenza progression in vaccinated and unvaccinated children and adults depending on the possible variants of its progression. In addition, to calculate QALY loss, the effect of disease on a patient’s quality of life was taken into account. Results. According to the budget impact analysis results, if school-aged children are vaccinated with coverage of 80%, the total cost stands at 7 140 383 360.87 tenges. In the case of refusal of vaccination among school – aged children, the total treatment costs for children with influenza will account for 8 589 133 135,95 tenges, with expenditures increased by 1 448 749 775,08 tenges. If adults (18 years of age and older) are vaccinated and 10% of the population is covered by immunization, the total cost will be 27 791 126 613.76 and 26 848 387 939.88 tenges, respectively. In the case of non-vaccination in adults, the total costs for the treatment of influenza will be 28 105 372 838,39 tenges, which is higher by 314 246 224,63 tenges than in the case of the population’s vaccination coverage of 10%, and by 1 256 984 898,51 tenges with vaccination coverage of 40%. Conclusion. In general, children and adults’ vaccination is not only a cost-effective but also a cost-saving method of preventing influenza in the health care system of Kazakhstan. Keywords: influenza vaccines, vaccination, clinical effectiveness, cost-effectiveness, cost-utility, children, adults

Description of Influenza B in seasonal epidemic in Cantabria during the beginning of the pandemia due to SARS-CoV-2

Introduction. Co-circulation of the two Influenza B lineages hinders forecast of strain to include in trivalent vaccine. Autonomous Communities such as Cantabria continue without supplying tetravalent vaccine. The aim of this study was to analyse epidemiological characteristics of influenza type B in Cantabria (2019-2020 season) as well as to establish the predominant lineage and its relation to the recommended vaccine. Methods. Retrospective study whereby flu diagnosis and lineage analysis were determined by RT-PCR. Results. All samples belonged to the Victoria lineage. Most prevalent viral co-infection was due to SARS-CoV-2. The population affected by influenza B was mainly paediatric and non-vaccinated patients more frequently required hospital admittance. Conclusions. Influenza type B has a higher incidence in the paediatric population and type A affects more the adult population. Only 28.8% of patients with Influenza B that presented with some underlying condition or risk factor were vaccinated. This shows the need to increase coverage with tetravalent vaccines in order to reduce the burden of disease associated with the Influenza B virus.

Vaccine Preperative Trial for Leptospirosis and their Pathological, Immunological Study by Serum Electrophoresis

Leptospirosis is a fatal infectious disease caused by different serovars of Leptospira spirochetes affecting humans and animals. In the present study, the trials of the whole-cell killed formalin treated monovalent vaccine using Leptospira icterohaemorrhagiae and trivalent vaccine using Leptospira icterohaemorrhagiae, Leptospira louisiana, and Leptospira hebdomadis were studied. The serum electrophoresis studies were done after administration of the vaccine into the experimental albino mice along with the booster dose of the vaccinated serum by densitometric readings. Similarly, the pathological observations were made by dissecting the virulent mice, vaccinated mice, and comparing them with the control mice. The MAT titre was also studied after the booster dose administration of the vaccinated serum. The monovalent and trivalent whole-cell killed formalin treated vaccines shows significant raise in the total proteins, albumin, globulin, α 1 globulin, α 2 globulin, β globulin and γ globulins of the serum as well as increase in significant levels in the antibody levels after the administration of the booster dose at an interval of 14 days. Keywords: Leptospira, Whole-cell killed formalin treated vaccine, Immunological study, Pathological study, Serum electrophoresis.