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1.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1560743

ABSTRACT

Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2-neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 107 TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P-immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Administration, Intranasal , Animals , Antibodies, Viral/blood , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Cricetinae , Genetic Vectors , Immunization , Parainfluenza Virus 3, Bovine/genetics , Parainfluenza Virus 3, Human/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
2.
Ital J Pediatr ; 47(1): 225, 2021 Nov 13.
Article in English | MEDLINE | ID: covidwho-1515449

ABSTRACT

BACKGROUND: In Italy only recently, for the 2020-21 season, has the flu vaccination been extended to all children. A quadrivalent live attenuated influenza vaccine (qLAIV) was administered to children aged 2-17 years for the first time. We registered the number and severity of adverse reactions to (Fluenz Tetra™) and the factors influencing them, evaluated uniformity of access to care and assessed the degree of satisfaction with the vaccination of both parents and health care providers, in order to improve the 2021-22 vaccination program. METHODS: On vaccination day, a questionnaire was given out to collect information about the children and their parents. Between 1 and 3 months later, the parents were contacted to record any adverse reactions following (Fluenz Tetra™) and rate the degree of satisfaction. RESULTS: We received data of 3226 children from 2152 families. Adverse events were reported in 24.8% of children: 80.6% mild, 18.1% moderate and 1.3% significant. The most common were rhinitis (52.5%) and fever (24.4%). Statistical analysis performed with a multiple regression model, showed that children aged 2-5 years have an increased risk of adverse events compared to both 6-10 years old (aRR 1.7, 95% CI 1.5-1.9, p < 0. 001) and 11-17 years old (aRR 1.5, 95% CI 1-2.2, p = 0.051). Most families chose to vaccinate their children to protect them and because they were concerned about Covid19. The main channel through which parents became aware of a new flu vaccination was word-of-mouth (39.8%), which occurred mostly among parents of the same school group, followed by information from the child's doctor (30.6%), the Internet (26.9%), personal research (15%), newspapers (4%), telecommunications (7.5%) and other (2.6%). Most parents (83.3%) were very satisfied and intend to vaccinate their children with qLAIV again (83.8%). The majority of operators (93%) considered the experience as excellent and are willing to repeat it (94.6%). CONCLUSION: (Fluenz Tetra™) proved to be easy to administer and the degree of satisfaction was high among both health workers and parents. Considering its substantial safety profile especially in school-age children and adolescents, all these aspects make the nasal qLAIV optimal for widespread immunization. Schools offer the best setting to reach more families and physicians should be actively involved.


Subject(s)
Influenza Vaccines/administration & dosage , Nasal Sprays , Adolescent , Child , Child, Preschool , Female , Humans , Italy , Vaccines, Attenuated/administration & dosage
3.
Pediatrics ; 148(4)2021 10.
Article in English | MEDLINE | ID: covidwho-1398985

ABSTRACT

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of the influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2021-2022 season. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during circulation of severe acute respiratory syndrome coronavirus 2, which is expected to continue during this influenza season. In this technical report, we summarize recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, vaccination coverage, and detailed guidance on storage, administration, and implementation. We also provide background on inactivated and live attenuated influenza vaccine recommendations, vaccination during pregnancy and breastfeeding, diagnostic testing, and antiviral medications for treatment and chemoprophylaxis.


Subject(s)
Influenza Vaccines , Influenza, Human/prevention & control , Antiviral Agents/therapeutic use , Breast Feeding , Child , Contraindications, Drug , Drug Resistance, Viral , Drug Storage , Female , Hospitalization , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Influenza, Human/mortality , Mass Vaccination , Risk Factors , United States/epidemiology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects
4.
Emerg Microbes Infect ; 10(1): 1626-1637, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1348038

ABSTRACT

Coronaviruses (CoVs) can infect a variety of hosts, including humans, livestock and companion animals, and pose a serious threat to human health and the economy. The current COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people. Unfortunately, effective treatments for CoVs infection are still lacking, suggesting the importance of coronavirus vaccines. Our previous work showed that CoV nonstuctural protein 14 (nsp14) functions as (guanine-N7)-methyltransferase (N7-MTase), which is involved in RNA cap formation. Moreover, we found that N7-MTase is well conserved among different CoVs and is a universal target for developing antivirals against CoVs. Here, we show that N7-MTase of CoVs can be an ideal target for designing live attenuated vaccines. Using murine hepatitis virus strain A59 (MHV-A59), a representative and well-studied model of coronaviruses, we constructed N7-MTase-deficient recombinant MHV D330A and Y414A. These two mutants are highly attenuated in mice and exhibit similar replication efficiency to the wild-type (WT) virus in the cell culture. Furthermore, a single dose immunization of D330A or Y414A can induce long-term humoral immune responses and robust CD4+ and CD8+ T cell responses, which can provide full protection against the challenge of a lethal-dose of MHV-A59. Collectively, this study provides an ideal strategy to design live attenuated vaccines for coronavirus by abolishing viral RNA N7-MTase activity. This approach may apply to other RNA viruses that encode their own conservative viral N7-methyltransferase.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Animals , COVID-19 Vaccines/administration & dosage , Cytokines/biosynthesis , Humans , Immunity, Cellular , Immunity, Humoral , Immunogenicity, Vaccine , Interferon Type I/biosynthesis , Male , Mice , Mutation , Vaccines, Attenuated/administration & dosage , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/immunology
5.
J Virol ; 95(4)2021 01 28.
Article in English | MEDLINE | ID: covidwho-1075935

ABSTRACT

Swine influenza A virus (swIAV) infection causes substantial economic loss and disease burden in humans and animals. The 2009 pandemic H1N1 (pH1N1) influenza A virus is now endemic in both populations. In this study, we evaluated the efficacy of different vaccines in reducing nasal shedding in pigs following pH1N1 virus challenge. We also assessed transmission from immunized and challenged pigs to naive, directly in-contact pigs. Pigs were immunized with either adjuvanted, whole inactivated virus (WIV) vaccines or virus-vectored (ChAdOx1 and MVA) vaccines expressing either the homologous or heterologous influenza A virus hemagglutinin (HA) glycoprotein, as well as an influenza virus pseudotype (S-FLU) vaccine expressing heterologous HA. Only two vaccines containing homologous HA, which also induced high hemagglutination inhibitory antibody titers, significantly reduced virus shedding in challenged animals. Nevertheless, virus transmission from challenged to naive, in-contact animals occurred in all groups, although it was delayed in groups of vaccinated animals with reduced virus shedding.IMPORTANCE This study was designed to determine whether vaccination of pigs with conventional WIV or virus-vectored vaccines reduces pH1N1 swine influenza A virus shedding following challenge and can prevent transmission to naive in-contact animals. Even when viral shedding was significantly reduced following challenge, infection was transmissible to susceptible cohoused recipients. This knowledge is important to inform disease surveillance and control strategies and to determine the vaccine coverage required in a population, thereby defining disease moderation or herd protection. WIV or virus-vectored vaccines homologous to the challenge strain significantly reduced virus shedding from directly infected pigs, but vaccination did not completely prevent transmission to cohoused naive pigs.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines/administration & dosage , Orthomyxoviridae Infections/transmission , Swine Diseases/transmission , Virus Shedding , Adjuvants, Immunologic/administration & dosage , Animals , Female , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/isolation & purification , Orthomyxoviridae Infections/prevention & control , Swine , Swine Diseases/prevention & control , Vaccination , Vaccines, Attenuated/administration & dosage , Vaccines, Inactivated/administration & dosage
6.
Nature ; 590(7845): 320-325, 2021 02.
Article in English | MEDLINE | ID: covidwho-953381

ABSTRACT

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Genetic Vectors/genetics , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Yellow Fever Vaccine/genetics , Animals , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/genetics , Cricetinae , Disease Models, Animal , Female , Glycosylation , Macaca fascicularis/genetics , Macaca fascicularis/immunology , Macaca fascicularis/virology , Male , Mesocricetus/genetics , Mesocricetus/immunology , Mesocricetus/virology , Mice , Safety , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/genetics
7.
Vet Immunol Immunopathol ; 225: 110061, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-828109

ABSTRACT

Our previous study demonstrated that ginseng stem-leaf saponins (GSLS) in combination with selenium (GSLS-Se) have adjuvant effect on the live vaccine of Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) in intraocular-and-intranasal immunization in chickens. The present study was to investigate the potential molecular mechanisms involved in the immunomodulation of GSLS-Se on the Harderian gland (HG). It was found that the window allowing animals susceptible to infections due to low antibody titers became smaller or even completely closed because of increased NDV-specific HI titers when NDV vaccine and GSLS-Se were coadministered for immunization at early life in chickens. In addition, NDV-specific sIgA and the numbers of IgG+, IgA+, IgM+ plasma cells were significantly more in GSLS-Se group than the control in the HGs. Transcriptome analysis of HGs identified 1184 differentially expressed genes (DEGs) between GSLS-Se treated and non-treated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses identified 42 significantly enriched GO terms and 13 canonical immune pathways. These findings indicated that GSLS-Se might exert immunomodulatory effects through influencing the antioxidant regulation and modulating the activity of immune related enzymes. Besides, Toll-like receptor (TLR) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway might be involved primarily in the immunomodulation. Therefore, enhanced antibody responses in GSLS-Se group may be attributed to the immunomodulatory effects of GSLS-Se on the immune-related gene profile expressed in the immunocompetent cells of the HGs.


Subject(s)
Harderian Gland/drug effects , Immunologic Factors/administration & dosage , Newcastle Disease/prevention & control , Panax/chemistry , Saponins/administration & dosage , Selenium/administration & dosage , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Animals , Antibodies, Viral/blood , Chickens , Female , Gene Expression Profiling , Newcastle Disease/immunology , Newcastle disease virus , Plant Leaves/chemistry , Saponins/immunology , Selenium/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Viral Vaccines/administration & dosage
8.
Microb Pathog ; 149: 104553, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-808667

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) causes an emerging and re-emerging coronavirus disease characterized by vomiting, acute diarrhea, dehydration, and up to 100% mortality in neonatal suckling piglets, leading to huge economic losses in the global swine industry. Vaccination remains the most promising and effective way to prevent and control PEDV. However, effective vaccines for PEDV are still under development. Understanding the genomic structure and function of PEDV and the influence of the viral components on innate immunity is essential for developing effective vaccines. In the current review, we systematically describe the recent developments in vaccine against PEDV and the roles of structural proteins, non-structural proteins and accessory proteins of PEDV in affecting viral virulence and regulating innate immunity, which will provide insight into the rational design of effective and safe vaccines for PEDV or other coronaviruses.


Subject(s)
Coronavirus Infections/veterinary , Porcine epidemic diarrhea virus/genetics , Porcine epidemic diarrhea virus/immunology , Swine Diseases/immunology , Swine Diseases/virology , Viral Vaccines/immunology , Animals , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Immunity, Innate , Porcine epidemic diarrhea virus/pathogenicity , Swine , Swine Diseases/prevention & control , Vaccination/veterinary , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Viral Proteins/genetics , Viral Vaccines/administration & dosage , Virulence
9.
Vaccine ; 38(45): 7146-7155, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-713091

ABSTRACT

BACKGROUND: COVID-19 pandemic has affected routine immunization globally. Impact will likely be higher in low and middle-income countries with limited healthcare resources and fragile health systems. We quantified the impact, spatial heterogeneity, and determinants for childhood immunizations of 48 million population affected in the Sindh province of Pakistan. METHODS: We extracted individual immunization records from real-time provincial Electronic Immunization Registry from September 23, 2019, to July 11, 2020. Comparing baseline (6 months preceding the lockdown) and the COVID-19 lockdown period, we analyzed the impact on daily immunization coverage rate for each antigen by geographical area. We used multivariable logistic regression to explore the predictors associated with immunizations during the lockdown. RESULTS: There was a 52.5% decline in the daily average total number of vaccinations administered during lockdown compared to baseline. The highest decline was seen for Bacille Cal-mette Guérin (BCG) (40.6% (958/2360) immunization at fixed sites. Around 8438 children/day were missing immunization during the lockdown. Enrollments declined furthest in rural districts, urban sub-districts with large slums, and polio-endemic super high-risk sub-districts. Pentavalent-3 (penta-3) immunization rates were higher in infants born in hospitals (RR: 1.09; 95% CI: 1.04-1.15) and those with mothers having higher education (RR: 1.19-1.50; 95% CI: 1.13-1.65). Likelihood of penta-3 immunization was reduced by 5% for each week of delayed enrollment into the immunization program. CONCLUSION: One out of every two children in Sindh province has missed their routine vaccinations during the provincial COVID-19 lockdown. The pool of un-immunized children is expanding during lockdown, leaving them susceptible to vaccine-preventable diseases. There is a need for tailored interventions to promote immunization visits and safe service delivery. Higher maternal education, facility-based births, and early enrollment into the immunization program continue to show a positive association with immunization uptake, even during a challenging lockdown.


Subject(s)
Coronavirus Infections/psychology , Measles/prevention & control , Pandemics , Pneumonia, Viral/psychology , Quarantine , Rotavirus Infections/prevention & control , Tuberculosis, Pulmonary/prevention & control , Vaccination/statistics & numerical data , BCG Vaccine/administration & dosage , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Electronic Data Processing , Female , Humans , Immunization Programs/statistics & numerical data , Infant , Infant, Newborn , Male , Measles/epidemiology , Measles/immunology , Measles Vaccine/administration & dosage , Pakistan/epidemiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Registries , Rotavirus Infections/epidemiology , Rotavirus Infections/immunology , Rotavirus Vaccines/administration & dosage , Rural Population , SARS-CoV-2 , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/immunology , Urban Population , Vaccination/psychology , Vaccination Coverage/statistics & numerical data , Vaccines, Attenuated/administration & dosage
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