RESUMO
Inactivated influenza A virus (IAV) vaccines help reduce clinical disease in suckling piglets, although endemic infections still exist. The objective of this study was to evaluate the detection of IAV in suckling and nursery piglets from IAV-vaccinated sows from farms with endemic IAV infections. Eight nasal swab collections were obtained from 135 two-week-old suckling piglets from four farms every other week from March to September 2013. Oral fluid samples were collected from the same group of nursery piglets. IAV RNA was detected in 1.64% and 31.01% of individual nasal swabs and oral fluids, respectively. H1N2 was detected most often, with sporadic detection of H1N1 and H3N2. Whole-genome sequences of IAV isolated from suckling piglets revealed an H1 hemagglutinin (HA) from the 1B.2.2.2 clade and N2 neuraminidase (NA) from the 2002A clade. The internal gene constellation of the endemic H1N2 was TTTTPT with a pandemic lineage matrix. The HA gene had 97.59% and 97.52% nucleotide and amino acid identities, respectively, to the H1 1B.2.2.2 used in the farm-specific vaccine. A similar H1 1B.2.2.2 was detected in the downstream nursery. These data demonstrate the low frequency of IAV detection in suckling piglets and downstream nurseries from farms with endemic infections in spite of using farm-specific IAV vaccines in sows.
Assuntos
Fazendas , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Filogenia , Doenças dos Suínos , Animais , Suínos , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/epidemiologia , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/classificação , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Animais Lactentes , Vacinação/veterinária , Doenças Endêmicas/veterinária , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , RNA Viral/genética , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H1N2/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/imunologia , Genoma ViralRESUMO
BACKGROUND: Influenza A virus (IAV) causes respiratory disease in pigs and is a major concern for public health. Vaccination of pigs is the most successful measure to mitigate the impact of the disease in the herds. Influenza-based virosome is an effective immunomodulating carrier that replicates the natural antigen presentation pathway and has tolerability profile due to their purity and biocompatibility. METHODS: This study aimed to develop a polyvalent virosome influenza vaccine containing the hemagglutinin and neuraminidase proteins derived from the swine IAVs (swIAVs) H1N1, H1N2 and H3N2 subtypes, and to investigate its effectiveness in mice as a potential vaccine for swine. Mice were immunized with two vaccine doses (1 and 15 days), intramuscularly and intranasally. At 21 days and eight months later after the second vaccine dose, mice were euthanized. The humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with a polyvalent influenza virosomal vaccine were investigated. RESULTS: Only intramuscular vaccination induced high hemagglutination inhibition (HI) titers. Seroconversion and seroprotection (> 4-fold rise in HI antibody titers, reaching a titer of ≥ 1:40) were achieved in 80% of mice (intramuscularly vaccinated group) at 21 days after booster immunization. Virus-neutralizing antibody titers against IAV were detected at 8 months after vaccination, indicating long-lasting immunity. Overall, mice immunized with the virosome displayed greater ability for B, effector-T and memory-T cells from the spleen to respond to H1N1, H1N2 and H3N2 antigens. CONCLUSIONS: All findings showed an efficient immune response against IAVs in mice vaccinated with a polyvalent virosome-based influenza vaccine.
Assuntos
Vacinas contra Influenza , Influenza Humana , Vacinas Virossomais , Lavagem Broncoalveolar , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H1N2 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Baço/citologia , Baço/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Virossomais/administração & dosagem , Vacinas Virossomais/imunologia , Virossomos/ultraestrutura , Humanos , Animais , CamundongosRESUMO
BACKGROUND: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. METHODS: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FINDINGS: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. INTERPRETATION: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FUNDING: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.
Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Imunização Secundária , Vacinas contra Influenza , SARS-CoV-2 , Vacinas de DNA , Administração Intranasal , Animais , COVID-19/genética , COVID-19/imunologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Chlorocebus aethiops , Modelos Animais de Doenças , Cães , Feminino , Células HEK293 , Humanos , Imunidade nas Mucosas , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Células VeroRESUMO
Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups-non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)-for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.
Assuntos
Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Memória Imunológica , Vacinas contra Influenza/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/virologia , Exercício Físico , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Masculino , VacinaçãoRESUMO
ABSTRACT: Observational studies indicate that vaccine-induced immunity can decline over time. However, few researchers have incorporated this kind of waning effect into their virus spread models. In this study, we simulate an influenza epidemic that considers the effects of waning immunity by fitting epidemiological models to CDC secondary historical data aggregated on a weekly basis, and derive the transmission rates at which susceptible individuals become infected over the course of the influenza season. Using a system of differential equations, we define four groups of individuals in a population: susceptible, vaccinated, infected, and recovered. We show that a larger number of initially infected individuals might not only bring the influenza season to an end sooner but also reduce the epidemic size. Moreover, any influenza virus that entails a faster recovery rate does not necessarily lead to a smaller epidemic size. We illustrate how simulation helps in understanding the effects of influenza epidemiological model in the presence of waning influenza vaccine immunity.
Assuntos
Surtos de Doenças , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Simulação por Computador , Humanos , Influenza Humana/prevenção & controle , Fatores de Tempo , Estados Unidos , VacinaçãoRESUMO
It's been almost a century since immunologists started using adjuvants as tools to develop more effective vaccines. Despite the rising number of adjuvanted vaccines in the last decades, we still lack knowledge of the adjuvants' effects on antibody response. This study was aimed to test the effect of immunizing mice with the human Inactivated Influenza vaccine (IIV), either alone or combined with different widely used adjuvants on the specific antibody response induced. Differential levels of IgM and IgG subclasses were found with the different adjuvants tested. Higher levels of antibodies did not always correspond with a higher efficacy to interfere with the virus infectivity. Differences in neutralization properties are possibly mediated by the specificity of the repertoire of antibodies induced. The repertoire was studied using a phage display 7-mer peptide library to screen for epitopes/mimotopes recognized by serum pools from vaccinated mice. The selected phage clones included peptides that corresponded to conformational mimotopes since they have no homology with lineal sequences of the Influenza strains' proteins. Five peptides were identified as recognized by sera from mice immunized with the IIV vaccine alone, including peptides from the hemagglutinin stalk domain, and by sera from mice immunized with the vaccine plus the different adjuvants employed. Adjuvants elicited a more diverse repertoire of epitope-recognizing antibodies that recognized epitopes of the HA recombinant globular head. Mimotopes were theoretically located at the neutralizing antigenic sites of the globular head of Influenza A H1N1pdm09, Influenza A H3N2, and Influenza B hemagglutinin. This study illustrates how different adjuvants can modify the extent and quality of humoral immunity against the IIV vaccine and the effectiveness of vaccination.
Assuntos
Adjuvantes Imunológicos/farmacologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra Influenza/imunologia , Potência de Vacina , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Biologia Computacional , Epitopos/imunologia , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Biblioteca de Peptídeos , VacinaçãoRESUMO
In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 µg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.
Assuntos
Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/biossíntese , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Animais , Antígenos Virais/biossíntese , Antígenos Virais/imunologia , Composição de Medicamentos/métodos , Composição de Medicamentos/estatística & dados numéricos , Indústria Farmacêutica/normas , Feminino , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Produtos Inativados/biossíntese , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/isolamento & purificaçãoRESUMO
Esta publicação, a 6ª da série LEIASS (Linha Editorial Internacional de Apoio aos Sistemas de Saúde), é fruto dos esforços conjuntos do Conselho Nacional de Secretários de Saúde do Brasil (CONASS) e do Instituto de Higiene e Medicina Tropical da Universidade Nova de Lisboa em reunir artigos de destacados autores, de diferentes países, sobre o importante tema da Comunicação em Saúde, nestes tempos de pandemia da Covid-19. Além de autores do Brasil e Portugal, estão também presentes neste volume artigos de especialistas do Canadá, Estados Unidos da América, Inglaterra, México e Uruguai, a quem agradecemos o valioso contributo à discussão. Um agradecimento especial deve ser feito à Profa. Dra. Ana Valéria Machado Mendonça, da Universidade de Brasília, que aceitou nosso convite para encarregar-se de organizar a presente obra. Há uma riqueza imensa de assuntos, que incluem a promoção da saúde; a revisão sistemática sobre o processo de comunicação em saúde na vigência da pandemia; a comunicação direcionada a povos indígenas; as questões afetas à saúde mental; a desinformação e o papel da mídia, dentre outros. Esperamos que a partilha de pontos de vista distintos, que envolvem realidades próprias a cada um desses países, possa auxiliar na compreensão do que se tem assistido em nível global em matéria de comunicação em saúde e suas repercussões no sucesso ou nas dificuldades enfrentadas face à pandemia da COVID-19.
Assuntos
Humanos , Pneumonia Viral/epidemiologia , Quarentena/organização & administração , Infecções por Coronavirus/epidemiologia , Pandemias/prevenção & controle , Monitoramento Epidemiológico , Sistemas Públicos de Saúde , Isolamento Social , Brasil/epidemiologia , Vacinas contra Influenza/imunologia , Programas de Imunização , Comunicação , Populações Vulneráveis , Influenza Humana/imunologia , Comunicação em Saúde , Promoção da Saúde/organização & administraçãoRESUMO
In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24-59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7. Several interferon-stimulated genes are differentially expressed in children with pre-LAIV asymptomatic respiratory viral infections and negatively correlated with LAIV VLs. Upregulation of genes enriched in macrophages, neutrophils, and eosinophils is associated with lower VLs and found more commonly in children with asymptomatic viral infections. Variability in pre-infection mucosal interferon gene expression in children may impact the course of subsequent influenza infections. This variability may be due to frequent respiratory viral infections, demonstrating the potential importance of mucosal virus-virus interactions in children.