Trivalent Vaccine Research Articles

Evaluation of Pre-Pandemic Trivalent COBRA HA Vaccine in Mice Pre-Immune to Historical H1N1 and H3N2 Influenza Viruses.

Initial exposure to influenza virus(es) during early childhood produces protective antibodies that may be recalled following future exposure to subsequent viral infections or vaccinations. Most influenza vaccine research studies use immunologically naïve animal models to assess vaccine effectiveness. However, most people have an extensive influenza immune history, with memory cells produced by viruses or vaccines representing multiple influenza viruses. In this study, we explored the effect influenza seasonal virus-induced immunity has on pre-pandemic influenza virus vaccination. The mice that were pre-immune to historical H1N1 and H3N2 seasonal influenza viruses were vaccinated with adjuvanted pre-pandemic (H2, H5, and H7) HA-based computationally optimized broadly reactive antigen (COBRA) vaccines, and were fully protected from lethal challenge, whereas the mock-vaccinated mice, with or without pre-immunity, were not protected from morbidity or mortality. Detectable antibody titers were present in the pre-immune mice vaccinated with a single dose of vaccine, but not in the immunologically naïve mice. The mice vaccinated twice with the trivalent COBRA HA vaccine had similar antibody titers regardless of their pre-immune status. Overall, seasonal pre-immunity did not interfere with the immune responses elicited by pre-pandemic COBRA HA vaccines or the protection against pre-pandemic viruses.

ADAPTATION OF FOOT & MOUTH DISEASE VIRUS SUBTYPES PAN ASIA-II, TUR-06 AND SINDH-08 TOWARDS THE VACCINE DEVELOPMENT AND SEROLOGICAL FINDINGS BY SPC ELISA AND SERUM NEUTRALIZATION TEST

FMD serotype “O” with subtype PAN Asia-II, serotype “A” with subtype Tur-06 and serotype “Asia-1” with subtype Sindh-08 were adapted on the LFBK cell line and subsequently on BHK-21. After inactivation these subtypes were introduced for the development of oil based trivalent vaccine against FMD. The study was conducted on the experimental animals (cow calves) at Livestock Production Research Institute (LPRI), Okara. Twenty one unvaccinated cattle calves of age group 4-6 month were used in the study, 16 were injected with experimentally prepared oil based FMD vaccine at the dose rate of 2cc per cow calf at day 0 and 28 post priming while five cattle calves were kept as control. The FMD oil based vaccine containing subtypes PAN ASIA-II, TUR-06 and SINDH-08 showed satisfactory immune response on ELISA and Serum Neutralization Test (SNT) at day 28 post priming and day 28 post booster. The study aimed to strengthen the national control strategy against FMD by the incorporation of prevalent field strains of FMD virus for the vaccine development.

Response to back-to-back outbreaks of circulating vaccine-derived poliovirus type 2 in two nomadic pastoralist settlements in Oti Region, Ghana-2019

BackgroundThe global switch from trivalent oral poliovirus vaccine (OPV) to bivalent OPV in April 2016 without corresponding co-administration of inactivated poliovirus vaccine (IPV) until June 2018, created a cohort of poliovirus type 2 naïve children with risk of developing vaccine-derived poliovirus type 2 (VDPV2). In November and December 2019, two cases of circulating vaccine-derived poliovirus type 2 (cVDPV2) were confirmed in quick succession through Acute Flaccid Paralysis (AFP) surveillance in two nomadic pastoralist settlements in Oti Region. We investigated to determine the outbreak extent, identify risk factors and implement control and preventive measures.MethodsWe interviewed case-patients’ families, abstracted immunization records, assessed AFP surveillance and conducted rapid OPV and IPV vaccination coverage surveys. Using AFP case definition of any child less than 15 years in the community with sudden onset of paralysis from July to November 2019 (in case-patient 1’s district) and August to December 2019 (in case-patient 2’s district), we conducted active case search. Stool samples from apparently healthy children and close contacts of the case-patients were collected and tested for poliovirus. We conducted environmental assessment of the community to identify potential risk factors.ResultsCase-patient 1 was an eight-year-old female who had taken two doses of OPV while case-patient 2 was an eight-month-old male who had taken three out of required four OPV doses in addition to IPV at seven months. Families of both case-patients had either travelled to or received visitors from areas with confirmed cVDPV2. Of all children surveyed, eight (29.6%) of 27 and three (18.8%) of 16 eligible children in communities of case-patient 1 and 2 respectively had received required four doses of OPV. No AFP case was found in both communities and surrounding settlements. Both communities had no source of potable water and toilet facilities. A stool sample from a contact of case-patient 1 tested positive for cVDPV2.ConclusionOutbreaks of cVDPV2 occurred in insanitary, under-vaccinated nomadic pastoralist settlements in Oti Region. Three rounds of monovalent OPV vaccination campaigns for children under 5 years of age in the districts and region as well as countrywide IPV vaccination campaign for poliovirus type 2 naïve cohort were conducted.

Characterization of a highly virulent Avibacterium paragallinarum isolate.

Infectious coryza (IC) is an important respiratory infectious disease in chickens. In this study, an Avibacterium paragallinarum Page serovar C strain, named ZJ-C, was isolated from a local layer flock that was routinely vaccinated with an inactivated trivalent vaccine, using reference strain Modesto as the serovar C immunogen. The pathogenicity, immunogenicity, and genetic characteristics of ZJ-C were studied. The minimum pathogenic dose of the isolate was 100 CFU, which was 1/1,000 of the dose of the serovar C reference strain Modesto. The vaccination-challenge trial in specific pathogen-free (SPF) chickens showed that the ZJ-C bacterin could provide 100% protection against challenge from both ZJ-C and Modesto strains, whereas Modesto provided 100% protection against challenge from itself, but only 70% protection against ZJ-C. Sequence analysis of the HMTp210 hypervariable region (region 2) showed that the homology of region 2 between ZJ-C and Modesto was 96.14%, whereas the homology between ZJ-C and the Kume serovar C-4 reference strain HP60 was 99.83%. Phylogenetic analysis of region 2 showed that ZJ-C was most closely related to cluster C-4, represented by HP60. The experimental data obtained in this study will help the selection of optimal vaccine strains and assist serotyping studies of Av. paragallinarum.

Preparation of novel trivalent vaccine against enterotoxigenic Escherichia coli for preventing newborn piglet diarrhea.

To develop a trivalent genetically engineered inactivated Escherichia coli vaccine (K88ac-3STa-LTB) that neutralizes the STa toxin by targeting fimbriae and entertoxins for the treatment of enterotoxigenic E coli. 18- to 22-g mice, rabbits, pregnant sows. Using PCR, the K88ac gene and LTB gene were cloned separately from the template C83902 plasmid. At the same time, the 3 STa mutant genes were also amplified by using the gene-directed mutation technology. Immune protection experiments were performed, and the minimum immune dose was determined in mice and pregnant sows. The ELISA test could be recognized by the STa, LTB, and K88ac antibodies. Intragastric administration in the suckling mouse confirmed that the protein had lost the toxicity of the natural STa enterotoxin. The results of the immune experiments showed that K88ac-3STa-LTB protein could stimulate rabbits to produce serum antibodies and neutralize the toxicity of natural STa enterotoxin. The efficacy test of the K88ac-3STa-LTB-inactivated vaccine showed that the immune protection rate of the newborn piglets could reach 85% on the first day after suckling. At the same time, it was determined that the minimum immunization doses for mice and pregnant sows were 0.2 and 2.5 mL, respectively. This research indicates that the K88ac-3STa-LTB trivalent genetically engineered inactivated vaccine provides a broad immune spectrum for E coli diarrhea in newborn piglets and prepares a new genetically engineered vaccine candidate strain for prevention of E coli diarrhea in piglets.

Seroprevalence of poliovirus antibodies in Nigeria: refining strategies to sustain the eradication effort.

in 2016, a switch from trivalent oral poliovirus vaccine (OPV) (containing serotypes 1,2,3) to bivalent OPV (types 1,3) was implemented globally. We assessed the seroprevalence of poliovirus antibody levels in selected Nigerian states, before and after the switch, documented poliovirus type2 outbreak responses conducted and ascertained factors associated with immunity gaps based on seroprevalence rates. we conducted a secondary analysis of stored serum samples from the 2018 Nigeria National HIV/AIDS Indicator and Impact Survey. Serum from 1,185 children aged 0-119 months residing in one southern and four northern states were tested for serotype-specific PV neutralizing antibodies; seropositivity was a reciprocal titer ≥8. We conducted regression analysis to determine sociodemographic risk factors associated with low seroprevalence using SAS 9.4. children aged 24-119 months (pre-switch cohort) had seroprevalence against PV1, PV2, and PV3, of 97.3% (95% CI:96.4-98.2), 93.8% (95% CI:92.2-95.5), and 91.3% (95% CI:89.2-93.4), while children aged <24 months (post-switch) had seroprevalence of 86.0% (95% CI:81.2-90.8), 55.6% (95% CI: 47.7-63.4), and 77.2% (95% CI:71.0-83.4) respectively. Regression analysis showed age <24 months was associated with lower seroprevalence against all PV serotypes, (p<0.0001); females had lower seroprevalence against PV1 (p=0.0184) and PV2 (p=0.0354); northern states lower seroprevalence against PV1 (p=0.0039), while well-water source lower seroprevalence against PV3 (p=0.0288). this study showed high seroprevalence rates against PV 1, 2, and 3 in pre-switch children (aged 24-119 months). However, post-switch children (<24 months) had low immunity against PV2 despite outbreak responses. Strategies to increase routine immunization coverage and high-quality polio campaigns can increase immunity against polio virus.

Immune response of European sea bass (Dicentrarchus labrax L.) against combination of antigens from three different pathogens

Three of the most important diseases of Mediterranean intensive European sea bass farming are, viral nervous necrosis (VNN) caused by the red grouper nervous necrosis virus (RGNNV) genotype of b-nodavirus, photobacteriosis caused by Photobacterium damselae subsp. piscicida (Phdp) and vibriosis caused mainly by the O1 serotype of Vibrio anguillarum (VaO1). Prevention against these diseases is performed through vaccination with a monovalent vaccine against the viral disease and, usually, with bivalent vaccines against the bacterial diseases. However, it is very difficult to program two vaccinations during the same season for the same fish stock and producers are forced to either vaccinate for the viral or the bacterial diseases or to perform double vaccination with both vaccines, without any prior knowledge on any interactions that may occur due to the plethora of antigens (Ag) injected. Ideally, therefore, a trivalent vaccine should be developed against all three diseases. The objective of this work was to analyse the immune response of sea bass against combinations of Ags from all three pathogens, namely viral particles, Phdp whole cells (WC), lipopolysaccharide (LPS), capsular polysaccharide (CPS) and extracellular products (ECPs) and VaO1 WC and ECPs in respect to the identification of any phenomena of immunodominance/immunosuppression between Ags with a view to select candidate Ags for inclusion in a trivalent vaccine formulation. Eight triplicate groups of fish were immunized with different combinations of the aforementioned Ags and another triplicate group served as negative control. Blood serum was isolated at various time-points post-immunization for the measurement of specific antibodies against each Ag and, in addition, leucocytes were isolated at day 29 post-immunization for analysis of various cellular activities. Results indicated that best levels of specific a-NNV virus antibodies (Abs) were produced when VaO1 ECPs were not included in the Ag combinations, in contrast to the leucocytes proliferation assay where best stimulation against NNV Ags was measured when VaO1 ECPs were present in Ag combinations. VaO1 ECPs apparently is a strong immunogen for both humoral and cellular responses but suppresses immunological reactions against the other Ags.VaO1 WC, Phdp LPS and ECPs raised good humoral immune responses in the groups with best responses against VNN Ags, but only VaO1 WC and Phdp ECPs provided good stimulation of leucocytes, with Phdp WC and CPS effecting either similar stimulation with untrained leucocytes (control groups) or down-stimulation. Results are discussed with a view to select Ags from all three pathogens for inclusion in trivalent vaccine against all three pathogens.

Immune responses and protective efficacy of a trivalent combination DNA vaccine based on oprL, oprF and flgE genes of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an infectious pathogenic bacteria infecting many different species of animals. Currently, it lacks a commercial vaccine. In this study, three monovalent DNA vaccines (poprL, poprF, and pflgE), three bivalent combination DNA vaccines (poprL+poprF, poprL+pflgE, poprF+pflgE), and a trivalent DNA vaccine (poprL+poprF+pflgE) were constructed. Consequently, we immunised chickens with these DNA vaccines and used inactivated vaccines as the positive controls. Then, the immune efficacy was evaluated through serum antibody detection, a lymphocyte proliferation assay, and cytokine concentration determination. Lastly, we assessed the protection rate through a challenge experiment. Following vaccination, the serum antibody levels induced using these DNA vaccines were different due to the different coating antigens. In the trivalent combination DNA vaccine group, we established that the lymphocyte proliferation (SI values), IFN-γ, IL-2, and IL-4 levels were significantly higher than those of the other six DNA vaccine groups and the inactivated vaccine group. However, the protection provided was slightly lower than that of the inactivated vaccine and higher than those of other DNA vaccines. The protection rate of poprL, poprF, pflgE, poprL+poprF, poprL+pflgE, poprF+pflgE, poprL+poprF+pflgE, and the inactivated vaccine were 50, 45, 60, 75, 80, 80, 90, and 95%, respectively. The results of this study indicated the trivalent DNA vaccine based on oprL, oprF and flgE genes represents a promising approach for the prevention of Pseudomonas aeruginosa infections.

Immunogenicity of Catch-Up Immunization with Conventional Inactivated Polio Vaccine among Japanese Adults.

Most Japanese adults are vaccinated twice with the Sabin trivalent oral polio vaccine. Booster vaccination is recommended for Japanese travelers to polio-endemic/high-risk countries. We assessed the catch-up immunization of healthy Japanese adults aged ≥20 years with two doses of standalone conventional inactivated polio vaccine (cIPV). Immunogenicity was evaluated by serum neutralization titers (pre-booster vaccination, 4-6 weeks after each vaccination) against type 1, 2, and 3 poliovirus strains. The participants were 61 healthy Japanese adults (26 men/35 women; mean age ± standard deviation age 35.8 ± 8.0 years). Seropositivity rates (percentage of participants with anti-poliovirus antibody titers ≥1:8) pre-vaccination were 88.5%, 95.1%, and 52.5% for Sabin strains (type 1, 2, and 3); 72.1%, 93.4%, and 31.1% for virulent poliovirus strains (type 1: Mahoney; type 2: MEF-1; and type 3: Saukett); and 93.4%, 93.4%, 93.4%, and 88.5% for type 2 vaccine-derived poliovirus strains (SV3128, SV3130, 11,196, and 11,198). After one cIPV dose, all seropositivity rates increased to 98.4-100.0%. After two cIPV doses, the seropositivity rates reached 100% for all strains. cIPV was well tolerated, with no safety concerns. Catch-up immunization with standalone cIPV induced robust immune responses in Japanese adults, indicating that one booster dose boosted serum-neutralizing antibodies to many strains.

Efficacy Studies against PCV-2 of a New Trivalent Vaccine including PCV-2a and PCV-2b Genotypes and Mycoplasma hyopneumoniae When Administered at 3 Weeks of Age.

This study aimed to evaluate the efficacy of a new trivalent vaccine containing inactivated Porcine Circovirus 1-2a and 1-2b chimeras and a Mycoplasma hyopneumoniae bacterin administered to pigs around 3 weeks of age. This trivalent vaccine has already been proved as efficacious in a split-dose regimen but has not been tested in a single-dose scenario. For this purpose, a total of four studies including two pre-clinical and two clinical studies were performed. Globally, a significant reduction in PCV-2 viraemia and faecal excretion was detected in vaccinated pigs compared to non-vaccinated animals, as well as lower histopathological lymphoid lesion plus PCV-2 immunohistochemistry scorings, and incidence of PCV-2-subclinical infection. Moreover, in field trial B, a significant increase in body weight and in average daily weight gain were detected in vaccinated animals compared to the non-vaccinated ones. Circulation of PCV-2b in field trial A and PCV-2a plus PCV-2d in field trial B was confirmed by virus sequencing. Hence, the efficacy of this new trivalent vaccine against a natural PCV-2a, PCV-2b or PCV-2d challenge was demonstrated in terms of reduction of histopathological lymphoid lesions and PCV-2 detection in tissues, serum and faeces, as well as improvement of production parameters.

Post-marketing surveillance study on influenza vaccine in South Korea using a nationwide spontaneous reporting database with multiple data mining methods

Safety profiles of the influenza vaccine and its subtypes are still limited. We aimed to address this knowledge gap using multiple data mining methods and calculated performance measurements to evaluate the precision of different detection methods. We conducted a post-marketing surveillance study between 2005 and 2019 using the Korea Adverse Event Reporting System database. Three data mining methods were applied: (a) proportional reporting ratio, (b) information component, and (c) tree-based scan statistics. We evaluated the performance of each method in comparison with the known adverse events (AEs) described in the labeling information. Compared to other vaccines, we identified 36 safety signals for the influenza vaccine, and 7 safety signals were unlabeled. In subtype-stratified analyses, application site disorders were reported more frequently with quadrivalent and cell-based vaccines, while a wide range of AEs were noted for trivalent and egg-based vaccines. Tree-based scan statistics showed well-balanced performance. Among the detected signals of influenza vaccines, narcolepsy requires special attention. A wider range of AEs were detected as signals for trivalent and egg-based vaccines. Although tree-based scan statistics showed balanced performance, complementary use of other techniques would be beneficial when large noise due to false positives is expected.

Understanding the Role of HLA Class I Molecules in the Immune Response to Influenza Infection and Rational Design of a Peptide-Based Vaccine.

Influenza A virus is a respiratory pathogen that is responsible for regular epidemics and occasional pandemics that result in substantial damage to life and the economy. The yearly reformulation of trivalent or quadrivalent flu vaccines encompassing surface glycoproteins derived from the current circulating strains of the virus does not provide sufficient cross-protection against mismatched strains. Unlike the current vaccines that elicit a predominant humoral response, vaccines that induce CD8+ T cells have demonstrated a capacity to provide cross-protection against different influenza strains, including novel influenza viruses. Immunopeptidomics, the mass spectrometric identification of human-leukocyte-antigen (HLA)-bound peptides isolated from infected cells, has recently provided key insights into viral peptides that can serve as potential T cell epitopes. The critical elements required for a strong and long-living CD8+ T cell response are related to both HLA restriction and the immunogenicity of the viral peptide. This review examines the importance of HLA and the viral immunopeptidome for the design of a universal influenza T-cell-based vaccine.

Evaluation of Seasonal Inactivated Influenza Vaccines Prophylactic Efficacy

Relevance. Seasonal flu vaccination is still the most effective way to protect against flu viruses and help to reduce the burden of flu illnesses. Another possible benefit is the impact of yearly vaccines on severity of breakthrough infection. In this regard, the issue of choosing safe vaccine with high immunogenicity becomes relevant.Aims. To evaluate the prophylactic efficacy of inactivated seasonal flu vaccines (quadrivalent subunit vaccine with adjuvant and trivalent vaccine) and reactogenicity of quadrivalent vaccine.Materials and methods. 491 cases were included in our study: 152 cases received adjuvanted quadrivalent subunit flu vaccine «Grippol Quadrivalent», 118 cases received trivalent inactivated flu vaccine and 221 cases who have received no vaccinations during 2018–2019 epidemic season.Results. inactivated vaccines showed high prophylactic efficacy in preventing seasonal influenza. Incidence of influenza and other viral respiratory disease cases was lowest in «Grippol Quadrivalent» group. Breakthrough influenza cases in individuals vaccinated with inactivated vaccine were predominantly mild, no severe cases were reported. The early post-vaccination period in «Grippol Quadrivalent» group showed no variation in adverse events with other vaccines.Conclusion. Adjuvanted quadrivalent subunit flu vaccine was the most efficacious in preventing influenza in 2018–2019 epidemic season.

Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy.

It has long been known that oncolytic viruses wield their therapeutic capability by priming an inflammatory state within the tumor and activating the tumor immune microenvironment, resulting in a multifaceted antitumor immune response. Vaccine-derived viruses, such as measles and mumps, have demonstrated promising potential for treating human cancer in animal models and clinical trials. However, the extensive cost of manufacturing current oncolytic viral products makes them far out of reach for most patients. Here by analyzing the impact of intratumoral (IT) administrations of the trivalent live attenuated measles, mumps, and rubella viruses (MMR) vaccine, we unveil the cellular and molecular basis of MMR-induced anti-cancer activity. Strikingly, we found that IT delivery of low doses of MMR correlates with tumor control and improved survival in murine hepatocellular cancer and colorectal cancer models via increased tumor infiltration of CD8+ granzyme B+ T-cells and decreased macrophages. Moreover, our data indicate that MMR activates key cellular effectors of the host's innate and adaptive antitumor immunity, culminating in an immunologically coordinated cancer cell death. These findings warrant further work on the potential for MMR to be repurposed as safe and cost-effective cancer immunotherapy to impact cancer patients globally.

Relative effectiveness of the adjuvanted vs non-adjuvanted seasonal influenza vaccines against severe laboratory-confirmed influenza among hospitalized Italian older adults

In this study, we aimed to investigate the relative vaccine effectiveness (rVE) of the MF59-adjuvanted trivalent (aTIV) and non-adjuvanted quadrivalent (QIVe) egg-based standard-dose vaccines against severe laboratory-confirmed influenza. This test-negative case-control study was conducted in a hospital setting during four recent Italian influenza seasons (from 2018/19 to 2021/22). The clinical outcome was severe acute respiratory infection (SARI) with laboratory confirmation diagnosed among subjects aged ≥65 years. rVE of aTIV versus QIVe was estimated through propensity score matching followed by logistic regression. The influenza virus circulated to a significant extent only during the 2018/19 and 2019/20 seasons. The final population included 512 vaccinated older adults, of which 83 were cases and 429 were test-negative controls. aTIV and QIVe users differed substantially from the point of view of several baseline characteristics. The propensity score adjusted rVE of aTIV vs QIVe was 59.2% (95% CI: 14.6%, 80.5%), 54.7% (95% CI: -28.7%, 84.0%) and 56.9% (95% CI: -7.8%, 82.8%) against any influenza, A(H1N1)pdm09 and A(H3N2), respectively. aTIV was more effective than QIVe in preventing laboratory-confirmed SARI. The benefits of aTIV may be obscured by confounding indication.

Effectiveness estimates for enhanced trivalent influenza vaccines in an aged care summer outbreak

An influenza outbreak occurred during summer (February 2019) in an aged-care facility in Sydney, Australia. Residents had not received the annual 2019 influenza vaccine while 76.7% had received 2018 influenza vaccines about 9 months prior. Overall, 2018 influenza vaccine effectiveness during this outbreak was high (93.6%). The effectiveness of the high-dose trivalent vaccine (HD-TIV) and adjuvanted trivalent (a-TIV) vaccine were 89.8% (95% confidence interval: 18.8%-98.7%) and 72.5% (95% confidence interval: −106.7%-96.3%) respectively. The differences in effectiveness between HD-TIV, a-TIV and SD-QIV, during the summer outbreak were not significant.

МАРКЕТИНГОВЫЙ АНАЛИЗ ВАКЦИН, ПРИМЕНЯЕМЫХ ДЛЯ ИММУНОПРОФИЛАКТИКИ ГРИППА В РЕСПУБЛИКЕ БАШКОРТОСТАН

The study of cases of infectious diseases detected for the first time in the Republic of Bashkortostan (RB) revealed that in the group of infectious diseases, the nature of which is well studied, but the system of effective measures to combat them has not yet been developed, the greatest increase in morbidity in 2020 compared to 2015 was observed for influenza - by 341.16%. Therefore, the topic of marketing analysis on vaccines used in influenza immunoprophylaxis is relevant and timely. The analysis of the range of vaccines for the prevention of influenza was carried out by us according to the pharmaceutical market of the Republic of Bashkortostan, taking into account the information of the information and analytical system «State Register of Medicines» (GRLS) as of 08/23/2022 and presented by the 4th generation (generations). It was found that in the 2020/2021 epidemic season, relative to the 2015/2016 epidemic season, with a general decrease in the range of vaccines in the pharmaceutical market of the Republic of Bashkortostan, there was a 30.00% increase in the share of trivalent vaccines and 10.84% increase in the share of quadrivalent vaccines, the effectiveness of which increases the antigenic coincidence of influenza virus lines, the amount of costs prevented. Within the framework of the National Calendar of Preventive Vaccinations in the Republic of Bashkortostan, the transition to quadrivalent vaccines for immunoprophylaxis was not carried out, however, these vaccines were purchased by the population and organizations of Republic of Bashkortostan in pharmaceutical organizations for additional funds.

A(H3N2) antigenic variation of influenza is associated with low vaccine efficacy in the early 2018 influenza season in Mexico City

ObjectivesWe evaluated the VE and the mutations of the viruses present in the Mexican population at the beginning of 2018. MethodsWe diagnosed influenza in outpatients with a high-performance Rapid Influenza Diagnostic Test (RIDT) qRT–PCR. Descriptive statistics were used to describe the study population, while the chi-square test was used to determine clinical variables. VE was analyzed through a negative test design. We sequenced the hemagglutinin (HA) gene, performed a phylogenetic analysis, and analyzed the nonsynonymous substitutions both in and outside antigenic sites. ResultsOf the 240 patients analyzed, 42.5% received the trivalent vaccine, and 37.5% were positive for influenza. The VE for the general population for any influenza virus type or subtype was 37.0%, while the VE for the predominant influenza A(H3N2) subtype was the lowest (19.7%). The phylogenetic analysis of HA showed the co-circulation of clades and subclades 3C.2a1, 3C.2a1b, 3C.2a2, 3C.2a2re, 3C.2a3, and 3C.3a with identities approximately 97-98% similar to the vaccine composition. ConclusionLow VE was related to the co-circulation of multiple clades and subclades of influenza A(H3N2), with sufficient genetic and phenotypic distance to allow for the infection of vaccinated individuals.

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery

BackgroundRecurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy. MethodsWe conducted a randomised phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary end-point was relapse-free survival. Secondary end-points included overall survival and serologic response. ResultsA total of 136 patients were randomised, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumours and 14% had ≥4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events were Grade ≤2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥20% of patients) were injection site reaction (89.7%), fatigue (44.1%) and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The 1-year relapse-free survival rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year overall survival rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable. ConclusionsA sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms.Clinicaltrials.gov identifier: NCT01141491

Combined Trivalent Vaccine for Young Horses

The horse strangles, rhinopneumonia, and salmonella abortion are most often recordedin the regions engaged in breeding herd horses. Young horses are most affected by these infectious diseases. Mortality among sick young animals can reach up to 22 % of the total livestock. Therefore, the prevention of viral and bacterial infections becomes relevant for herd horse breeding.The paper presents data on preclinical and clinical trials, the effect on the body's natural resistance, the study of the effectiveness of the combined trivalent vaccine in laboratory animals and young horses. Preclinical testing of the vaccine on linear and outbred mice showed the absence of toxicity and pyrogenicity in rabbits. Experimental infection with the rhinopneumonia virus of vaccinated linear mice protected 88,8 %, and outbred white mice from infection with pathogens of salmonella abortion and the horse strangles 100 % of immunized mice. A clinical trial of a combined trivalent vaccine on young horses (657 heads) showed the effectiveness of preventive immunization in horse breeding farms that are disadvantaged for infectious diseases. Vaccination protected from the disease in 94-100 % of vaccinated animals. In a serological study of immunized young animals, the titer of antibodies to the rhinopneumonia virus was 1:3200-1:6400, agglutinating to the causative agent of salmonella abortion - 1:800-1:1600, and precipitating antibodies to the horse strangles streptococcus - 1:100. An increase in the content of the gamma globulin fraction in vaccinated animals was observed in a biochemical study of blood sera from young horses. Among those immunized with the combined vaccine, 4 heads (4,94 %) fell ill with the horse strangles, and 8 animals (7,21 %) among vaccinated. 62 heads (84,93 %) fell ill from the 73 heads of unvaccinated young animals. They were observed for clinical respiratory disease. For the treatment of patients, the probiotic preparation "Sakhabactisubtil" was used intranasally at a dose of 10 ml per head in combination with intramuscular administration of a fugat from a strain of bacteria Bacillus subtilis.Thus, a single administration of a combined trivalent vaccine for prophylactic purposes protects young herd breeding horses from the disease and thereby contributes to the safety of the livestock of horse breeding farms.