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2.
J Virol ; 96(18): e0133722, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36069551

RESUMO

COVID-19 and influenza are both highly contagious respiratory diseases that have been serious threats to global public health. It is necessary to develop a bivalent vaccine to control these two infectious diseases simultaneously. In this study, we generated three attenuated replicating recombinant vesicular stomatitis virus (rVSV)-based vaccine candidates against both SARS-CoV-2 and influenza viruses. These rVSV-based vaccines coexpress SARS-CoV-2 Delta spike protein (SP) bearing the C-terminal 17 amino acid (aa) deletion (SPΔC) and I742A point mutation, or the SPΔC with a deletion of S2 domain, or the RBD domain, and a tandem repeat harboring four copies of the highly conserved influenza M2 ectodomain (M2e) that fused with the Ebola glycoprotein DC-targeting/activation domain. Animal immunization studies have shown that these rVSV bivalent vaccines induced efficient humoral and cellular immune responses against both SARS-CoV-2 SP and influenza M2 protein, including high levels of neutralizing antibodies against SARS-CoV-2 Delta and other variant SP-pseudovirus infections. Importantly, immunization of the rVSV bivalent vaccines effectively protected hamsters or mice against the challenges of SARS-CoV-2 Delta variant and lethal H1N1 and H3N2 influenza viruses and significantly reduced respiratory viral loads. Overall, this study provides convincing evidence for the high efficacy of this bivalent vaccine platform to be used and/or easily adapted to produce new vaccines against new or reemerging SARS-CoV-2 variants and influenza A virus infections. IMPORTANCE Given that both COVID-19 and influenza are preferably transmitted through respiratory droplets during the same seasons, it is highly advantageous to develop a bivalent vaccine that could simultaneously protect against both COVID-19 and influenza. In this study, we generated the attenuated replicating recombinant vesicular stomatitis virus (rVSV)-based vaccine candidates that target both spike protein of SARS-Cov-2 Delta variant and the conserved influenza M2 domain. Importantly, these vaccine candidates effectively protected hamsters or mice against the challenges of SARS-CoV-2 Delta variant and lethal H1N1 and H3N2 influenza viruses and significantly reduced respiratory viral loads.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Vacinas Combinadas , Estomatite Vesicular , Aminoácidos/genética , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Cricetinae , Glicoproteínas/genética , Glicoproteínas/imunologia , Humanos , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Camundongos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Combinadas/imunologia , Vacinas Sintéticas/genética , Vesiculovirus/imunologia
3.
J Virol ; 96(19): e0100622, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36106872

RESUMO

Intranasal vaccination offers the potential advantage of needle-free prevention of respiratory pathogens such as influenza viruses with induction of mucosal immune responses. Optimal design of adjuvants and antigen delivery vehicles for intranasal delivery has not yet been well established. Here, we report that an adjuvant-containing nanoliposome antigen display system that converts soluble influenza hemagglutinin antigens into nanoparticles is effective for intranasal immunization. Intranasal delivery of nanoliposomes in mice delivers the particles to resident immune cells in the respiratory tract, inducing a mucosal response in the respiratory system as evidenced by nasal and lung localized IgA antibody production, while also producing systemic IgG antibodies. Intranasal vaccination with nanoliposome particles decorated with nanogram doses of hemagglutinin protected mice from homologous and heterologous H3N2 and H1N1 influenza virus challenge. IMPORTANCE A self-assembling influenza virus vaccine platform that seamlessly converts soluble antigens into nanoparticles is demonstrated with various H1N1 and H3N2 influenza antigens to protect mice against influenza virus challenge following intranasal vaccination. Mucosal immune responses following liposome delivery to lung antigen-presenting cells are demonstrated.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza , Imunidade nas Mucosas , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Adjuvantes Imunológicos , Administração Intranasal , Animais , Anticorpos Antivirais/imunologia , Células Apresentadoras de Antígenos/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Lipossomos , Camundongos , Nanopartículas , Infecções por Orthomyxoviridae/prevenção & controle , Vacinação
4.
PLoS Pathog ; 18(8): e1010755, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36006890

RESUMO

Annual influenza vaccination is recommended to update the variable hemagglutinin antigens. Here, we first designed a virus-like particle (VLP) displaying consensus multi-neuraminidase (NA) subtypes (cN1, cN2, B cNA) and M2 ectodomain (M2e) tandem repeat (m-cNA-M2e VLP). Vaccination of mice with m-cNA-M2e VLP induced broad NA inhibition (NAI), and M2e antibodies as well as interferon-gamma secreting T cell responses. Mice vaccinated with m-cNA-M2e VLP were protected against influenza A (H1N1, H5N1, H3N2, H9N2, H7N9) and influenza B (Yamagata and Victoria lineage) viruses containing substantial antigenic variations. Protective immune contributors include cellular and humoral immunity as well as antibody-dependent cellular cytotoxicity. Furthermore, comparable cross protection by m-cNA-M2e VLP vaccination was induced in aged mice. This study supports a novel strategy of developing a universal vaccine against influenza A and B viruses potentially in both young and aged populations by inducing multi-NA subtype and M2e immunity with a single VLP entity.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Anticorpos Antivirais , Humanos , Vírus da Influenza A/classificação , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Proteínas da Matriz Viral/genética
6.
J Virol ; 96(15): e0068922, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35862698

RESUMO

Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as new variants continue to emerge, periodic (and perhaps annual) vaccination will likely be recommended. New seasonal influenza virus vaccines currently need to be developed every year due to continual antigenic drift, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting both influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed an influenza A virus (IAV) genetic platform that allows the incorporation of an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicited neutralizing antibodies and provided protection from lethal challenge with both pathogens in mice. This approach may allow the leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses. IMPORTANCE The rapid emergence of SARS-CoV-2 variants since the onset of the pandemic has highlighted the need for both periodic vaccination "boosts" and a platform that can be rapidly reformulated to manufacture new vaccines. In this work, we report an approach that can utilize current influenza vaccine manufacturing infrastructure to generate combination vaccines capable of protecting from both influenza virus- and SARS-CoV-2-induced disease. The production of a combined influenza/SARS-CoV-2 vaccine may represent a practical solution to boost immunity to these important respiratory viruses without the increased cost and administration burden of multiple independent vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , SARS-CoV-2 , Vacinas Combinadas , Vírion , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Humanos , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , SARS-CoV-2/classificação , SARS-CoV-2/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
7.
J Immunol ; 209(1): 5-15, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35697384

RESUMO

Computationally optimized broadly reactive Ag (COBRA) hemagglutinin (HA) immunogens have previously been generated for several influenza subtypes to improve vaccine-elicited Ab breadth. As nearly all individuals have pre-existing immunity to influenza viruses, influenza-specific memory B cells will likely be recalled upon COBRA HA vaccination. We determined the epitope specificity and repertoire characteristics of pre-existing human B cells to H1 COBRA HA Ags. Cross-reactivity between wild-type HA and H1 COBRA HA proteins P1, X6, and Y2 were observed for isolated mAbs. The mAbs bound five distinct epitopes on the pandemic A/California/04/2009 HA head and stem domains, and most mAbs had hemagglutination inhibition and neutralizing activity against 2009 pandemic H1 strains. Two head-directed mAbs, CA09-26 and CA09-45, had hemagglutination inhibition and neutralizing activity against a prepandemic H1 strain. One mAb, P1-05, targeted the stem region of H1 HA, but did not compete with a known stem-targeting H1 mAb. We determined that mAb P1-05 recognizes a recently discovered HA epitope, the anchor epitope, and we identified similar mAbs using B cell repertoire sequencing. In addition, the trimerization domain distance from HA was critical to recognition of this epitope by mAb P1-05, suggesting the importance of protein design for vaccine formulations. Overall, these data indicate that seasonally vaccinated individuals possess a population of functional H1 COBRA HA-reactive B cells that target head, central stalk, and anchor epitopes, and they demonstrate the importance of structure-based assessment of subunit protein vaccine candidates to ensure accessibility of optimal protein epitopes.


Assuntos
Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vacinas contra Influenza , Influenza Humana , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Epitopos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle
8.
Vet Microbiol ; 271: 109491, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35714529

RESUMO

Viral infectious pathogens, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, can cause extremely high infection rates and mortality in humans. Therefore, it is urgent to develop an effective vaccine against coronavirus and influenza virus infection. Herein, we used the influenza virus as a vector to express the SARS-CoV-2 spike receptor-binding domain (RBD) and hemagglutinin-esterase-fusion (HEF) protein of the influenza C virus. We then evaluated the feasibility and effectiveness of this design strategy through experiments in vitro and in vivo. The results showed that the chimeric viruses could stably express the HEF protein and the SARS-CoV-2 spike RBD at a high level. BALB/c mice, infected with the chimeric virus, exhibited mild clinical symptoms, yet produced high specific antibody levels against RBD and HEF, including neutralizing antibodies. Importantly, high neutralizing antibodies could be retained in the sera of mice for at least 20 weeks. Altogether, our data provided a new strategy for developing safe and effective COVID-19 and influenza virus vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , Orthomyxoviridae , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra Influenza/imunologia , Camundongos , Camundongos Endogâmicos BALB C , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
9.
Vaccine ; 40(32): 4412-4423, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35680500

RESUMO

In response to immune pressure, influenza viruses evolve, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response capable of recognizing multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the efficacy and immunogenicity of mRNA vaccines encoding either the conserved stem domain of a group 1 hemagglutinin (HA), a group 2 nucleoprotein (NP), or a combination of the two antigens in mice, as well as evaluated immunogenicity in naïve and influenza seropositive nonhuman primates (NHPs). HA stem-immunized animals developed a robust anti-stem antibody binding titer, and serum antibodies recognized antigenically distinct group 1 HA proteins. These antibodies showed little to no neutralizing activity in vitro but were active in an assay measuring induction of antibody-dependent cellular cytotoxicity. HA-directed cell-mediated immunity was weak following HA stem mRNA vaccination; however, robust CD4 and CD8 T cell responses were detected in both mice and NHPs after immunization with mRNA vaccines encoding NP. Both HA stem and NP mRNA vaccines partially protected mice from morbidity following lethal influenza virus challenge, and superior efficacy against two different H1N1 strains was observed when the antigens were combined. In vivo T cell depletion suggested that anti-NP cell-mediated immunity contributed to protection in the mouse model. Taken together, these data show that mRNA vaccines encoding conserved influenza antigens, like HA stem and NP in combination, induce broadly reactive humoral responses as well as cell-mediated immunity in mice and NHPs, providing protection against homologous and heterologous influenza infection in mice.


Assuntos
Imunidade Celular , Imunidade Humoral , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Vacinas de mRNA , Animais , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza/imunologia , Camundongos , Nucleoproteínas/genética , Infecções por Orthomyxoviridae/prevenção & controle , Primatas , Vacinas Sintéticas , Vacinas de mRNA/imunologia
10.
Sci Rep ; 12(1): 9198, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35654904

RESUMO

The effects of adjuvants for increasing the immunogenicity of influenza vaccines are well known. However, the effect of adjuvants on increasing the breadth of cross-reactivity is less well understood. In this study we have performed a systematic screen of different toll-like receptor (TLR) agonists, with and without a squalene-in-water emulsion on the immunogenicity of a recombinant trimerized hemagglutinin (HA) vaccine in mice after single-dose administration. Antibody (Ab) cross-reactivity for other variants within and outside the immunizing subtype (homosubtypic and heterosubtypic cross-reactivity, respectively) was assessed using a protein microarray approach. Most adjuvants induced broad IgG profiles, although the response to a combination of CpG, MPLA and AddaVax (termed 'IVAX-1') appeared more quickly and reached a greater magnitude than the other formulations tested. Antigen-specific plasma cell labeling experiments show the components of IVAX-1 are synergistic. This adjuvant preferentially stimulates CD4 T cells to produce Th1>Th2 type (IgG2c>IgG1) antibodies and cytokine responses. Moreover, IVAX-1 induces identical homo- and heterosubtypic IgG and IgA cross-reactivity profiles when administered intranasally. Consistent with these observations, a single-cell transcriptomics analysis demonstrated significant increases in expression of IgG1, IgG2b and IgG2c genes of B cells in H5/IVAX-1 immunized mice relative to naïve mice, as well as significant increases in expression of the IFNγ gene of both CD4 and CD8 T cells. These data support the use of adjuvants for enhancing the breath and durability of antibody responses of influenza virus vaccines.


Assuntos
Vacinas contra Influenza , Influenza Humana , Vacinas Sintéticas/imunologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Animais , Anticorpos Antivirais , Hemaglutininas , Humanos , Imunoglobulina G/química , Vacinas contra Influenza/imunologia , Camundongos , Camundongos Endogâmicos BALB C
11.
J Virol ; 96(12): e0032022, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35638848

RESUMO

Vaccination against influenza virus infection can protect the vaccinee and also reduce transmission to contacts. Not all types of vaccines induce sterilizing immunity via neutralizing antibodies; some instead permit low-level, transient infection. There has been concern that infection-permissive influenza vaccines may allow continued spread in the community despite minimizing symptoms in the vaccinee. We have explored that issue for a universal influenza vaccine candidate that protects recipients by inducing T cell responses and nonneutralizing antibodies. Using a mouse model, we have shown previously that an adenoviral vectored vaccine expressing nucleoprotein (NP) and matrix 2 (M2) provides broad protection against diverse strains and subtypes of influenza A viruses and reduces transmission to contacts in an antigen-specific manner. Here, we use this mouse model to further explore the mechanism and features of that reduction in transmission. Passive immunization did not reduce transmission from infected donors to naive contact animals to whom passive serum had been transferred. Vaccination of antibody-deficient mIgTg-JHD-/- mice, which have intact T cell responses and antigen presentation, reduced transmission in an antigen-specific manner, despite the presence of some virus in the lungs and nasal wash, pointing to a role for cellular immunity. Vaccination at ages ranging from 8 to 60 weeks was able to achieve reduction in transmission. Finally, the immune-mediated reduction in transmission persisted for at least a year after a single-dose intranasal vaccination. Thus, this infection-permissive vaccine reduces virus transmission in a long-lasting manner that does not require antibodies. IMPORTANCE Universal influenza virus vaccines targeting antigens conserved among influenza A virus strains can protect from severe disease but do not necessarily prevent infection. Despite allowing low-level infection, intranasal immunization with adenovirus vectors expressing the conserved antigens influenza nucleoprotein (A/NP) and M2 reduces influenza virus transmission from vaccinated to unvaccinated contact mice. Here, we show that antibodies are not required for this transmission reduction, suggesting a role for T cells. We also show that transmission blocking could be achieved in recipients of different ages and remained effective for at least a year following a single-dose vaccination. Such vaccines could have major public health impacts by limiting viral transmission in the community.


Assuntos
Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Adenoviridae , Animais , Anticorpos Antivirais , Humanos , Imunidade Celular , Vírus da Influenza A/genética , Vacinas contra Influenza/imunologia , Influenza Humana , Proteínas do Nucleocapsídeo/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/transmissão , Linfócitos T/imunologia , Vacinação , Proteínas da Matriz Viral/imunologia , Proteínas Viroporinas/imunologia
12.
J Virol ; 96(9): e0033222, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35446141

RESUMO

Influenza virus neuraminidase (NA)-targeting antibodies are an independent correlate of protection against influenza. Antibodies against the NA act by blocking enzymatic activity, preventing virus release and transmission. As we advance the development of improved influenza virus vaccines that incorporate standard amounts of NA antigen, it is important to identify the antigenic targets of human monoclonal antibodies (mAbs). Here, we describe escape mutants generated by serial passage of A/Netherlands/602/2009 (H1N1)pdm09 in the presence of human anti-N1 mAbs. We observed escape mutations on the head domain of the N1 protein around the enzymatic site (S364N, N369T, and R430Q) and also detected escape mutations located on the sides and bottom of the NA (N88D, N270D, and Q313K/R). This work increases our understanding of how human antibody responses target the N1 protein. IMPORTANCE As improved influenza virus vaccines are being developed, the influenza virus neuraminidase (NA) is becoming an important new target for immune responses. By identifying novel epitopes of anti-NA antibodies, we can improve vaccine design. Additionally, characterizing escape mutations in these epitopes aids in identifying NA antigenic drift in circulating viruses.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Anticorpos Monoclonais , Anticorpos Antivirais/metabolismo , Epitopos/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/genética , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Influenza Humana/virologia , Mutação , Neuraminidase/química , Neuraminidase/genética , Neuraminidase/imunologia
13.
J Virol ; 96(7): e0165221, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35289635

RESUMO

Commercial influenza virus vaccines often elicit strain-specific immune responses and have difficulties preventing illness caused by antigenically drifted viral variants. In the last 20 years, the H3N2 component of the annual vaccine has been updated nearly twice as often as the H1N1 component, and in 2019, a mismatch between the wild-type (WT) H3N2 vaccine strain and circulating H3N2 influenza strains led to a vaccine efficacy of ∼9%. Modern methods of developing computationally optimized broadly reactive antigens (COBRAs) for H3N2 influenza viruses utilize current viral surveillance information to design more broadly reactive vaccine antigens. Here, 7 new recombinant hemagglutinin (rHA) H3 COBRA hemagglutinin (HA) antigens were evaluated in mice. Subsequently, two candidates, J4 and NG2, were selected for further testing in influenza-preimmune animals based on their ability to elicit broadly reactive antibodies against antigenically drifted H3N2 viral isolates. In the preimmune model, monovalent formulations of J4 and NG2 elicited broadly reactive antibodies against recently circulating H3N2 influenza viruses from 2019. Bivalent mixtures of COBRA H1 and H3 rHA, Y2 + J4, and Y2 + NG2 outperformed multiple WT H1+H3 bivalent rHA mixtures by eliciting seroprotective antibodies against H1N1 and H3N2 isolates from 2009 to 2019. Overall, the newly generated COBRA HA antigens, namely, Y2, J4, and NG2, had the ability to induce broadly reactive antibodies in influenza-naive and preimmune animals in both monovalent and bivalent formulations, and these antigens outperformed H1 and H3 WT rHA vaccine antigens by eliciting seroprotective antibodies against panels of antigenically drifted historical H1N1 and H3N2 vaccine strains from 2009 to 2019. IMPORTANCE Standard-of-care influenza virus vaccines are composed of a mixture of antigens from different influenza viral subtypes. For the first time, lead COBRA H1 and H3 HA antigens, formulated as a bivalent vaccine, have been investigated in animals with preexisting immunity to influenza viruses. The cocktail of COBRA HA antigens elicited more broadly reactive anti-HA antibodies than those elicited by a comparator bivalent wild-type HA vaccine against H1 and H3 influenza viruses isolated between 2009 and 2019.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Vacinas Combinadas , Animais , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Camundongos , Infecções por Orthomyxoviridae/imunologia , Vacinas Combinadas/imunologia , Vacinas Sintéticas/imunologia
14.
Am J Kidney Dis ; 80(3): 309-318, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35288216

RESUMO

RATIONALE & OBJECTIVE: High-dose influenza vaccine provides better protection against influenza infection in older adults than standard-dose vaccine. We compared vaccine seroresponse among hemodialysis patients over a period of 4 months after administration of high-dose trivalent inactivated (HD-IIV3), standard-dose quadrivalent inactivated (SD-IIV4), or quadrivalent recombinant quadrivalent (RIV4) influenza vaccine. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Patients at 4 hemodialysis clinics who received influenza vaccine. EXPOSURE: Type of influenza vaccine. OUTCOME: Hemagglutination inhibition (HI) titers were measured at baseline and at 1, 2, 3, and 4 months after vaccination. The primary outcome was seroprotection rates at HI titers of at least 1:40 and at least 1:160 (antibody levels providing protection from infection in approximately 50% and 95% of immunocompetent individuals, respectively) at 1, 2, 3, and 4 months after vaccination. ANALYTICAL APPROACH: We calculated geometric mean titer as well as seroprotection and seroconversion rates. Adjusted generalized linear models with additional trend analyses were performed to evaluate the association between vaccine type and outcomes. RESULTS: 254 hemodialysis patients were vaccinated against influenza with HD-IIV3 (n = 141), SD-IIV4 (n = 36), or RIV4 (n = 77). A robust initial seroresponse to influenza A strains was observed after all 3 vaccines. Geometric mean titer and seroprotection (HI titer ≥1:160) rates against influenza A strains were higher and more sustained with HD-IIV3 than SD-IIV4 or RIV4. More than 80% of patients vaccinated with HD-IIV3 were seroprotected (HI titer ≥1:160) at month 4 (P < 0.001), whereas, among patients vaccinated with SD-IIV4 or RIV4, seroprotection rates were similar to those at baseline. Seroprotection rates were lower against B strains for all vaccines. LIMITATIONS: Because of the use of observational data, bias from unmeasured confounders may exist. Some age subgroups were small in number. Clinical outcome data were not available. CONCLUSIONS: Hemodialysis patients exhibited high seroprotection rates after all 3 influenza vaccines. The seroresponse waned more slowly with HD-IIV3 compared with SD-IIV4 and RIV4 vaccines.


Assuntos
Vacinas contra Influenza , Influenza Humana , Diálise Renal , Idoso , Anticorpos Antivirais/sangue , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Vacinas de Produtos Inativados
15.
Proc Natl Acad Sci U S A ; 119(13): e2025607119, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35320040

RESUMO

SignificanceAlthough the need for a universal influenza vaccine has long been recognized, only a handful of candidates have been identified so far, with even fewer advancing in the clinical pipeline. The 24-amino acid ectodomain of M2 protein (M2e) has been developed over the past two decades. However, M2e-based vaccine candidates have shortcomings, including the need for several administrations and the lack of sustained antibody titers over time. We report here a vaccine targeting strategy that has the potential to confer sustained and strong protection upon a single shot of a small amount of M2e antigen. The current COVID-19 pandemic has highlighted the importance of developing versatile, powerful platforms for the rapid deployment of vaccines against any incoming threat.


Assuntos
COVID-19 , Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Proteínas da Matriz Viral , Proteínas Viroporinas , Animais , Anticorpos Monoclonais/genética , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Células Dendríticas/imunologia , Humanos , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Pandemias/prevenção & controle , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/imunologia , Proteínas Viroporinas/imunologia
16.
Front Immunol ; 13: 782198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185881

RESUMO

Misunderstanding temporal coincidence of adverse events during mass vaccination and invalid assessment of possible safety concerns have negative effects on immunization programs, leading to low immunization coverage. We conducted this systematic review and meta-analysis to identify the incidence rates of GBS that are temporally associated with viral vaccine administration but might not be attributable to the vaccines. By literature search in Embase and PubMed, we included 48 publications and 2,110,441,600 participants. The pooled incidence rate of GBS was 3.09 per million persons (95% confidence interval [CI]: 2.67 to 3.51) within six weeks of vaccination, equally 2.47 per 100,000 person-year (95%CI: 2.14 to 2.81). Subgroup analyses illustrated that the pooled rates were 2.77 per million persons (95%CI: 2.47 to 3.07) for individuals who received the influenza vaccine and 2.44 per million persons (95%CI: 0.97 to 3.91) for human papillomavirus (HPV) vaccines, respectively. Our findings evidence the GBS-associated safety of virus vaccines. We present a reference for the evaluation of post-vaccination GBS rates in mass immunization campaigns, including the SARS-CoV-2 vaccine.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/epidemiologia , Vacinas contra Influenza/efeitos adversos , Vacinação em Massa/efeitos adversos , Vacinas contra Papillomavirus/efeitos adversos , Alphapapillomavirus/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vigilância da População , SARS-CoV-2/imunologia
18.
Viruses ; 14(2)2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35216022

RESUMO

Avian influenza virus remains a threat for humans, and vaccines preventing both avian and human influenza virus infections are needed. Since virus-like particles (VLPs) expressing single neuraminidase (NA) subtype elicited limited heterosubtypic protection, VLPs expressing multiple NA subtypes would enhance the extent of heterosubtypic immunity. Here, we generated avian influenza VLP vaccines displaying H5 hemagglutinin (HA) antigen with or without avian NA subtypes (N1, N6, N8) in different combinations. BALB/c mice were intramuscularly immunized with the VLPs to evaluate the resulting homologous and heterosubtypic immunity upon challenge infections with the avian and human influenza viruses (A/H5N1, A/H3N2, A/H1N1). VLPs expressing H5 alone conferred homologous protection but not heterosubtypic protection, whereas VLPs co-expressing H5 and NA subtypes elicited both homologous and heterosubtypic protection against human influenza viruses in mice. We observed that VLP induced neuraminidase inhibitory activities (NAI), virus-neutralizing activity, and virus-specific antibody (IgG, IgA) responses were strongly correlated with the number of different NA subtype expressions on the VLPs. VLPs expressing all 3 NA subtypes resulted in the highest protection, indicated by the lowest lung titer, negligible body weight changes, and survival in immunized mice. These results suggest that expressing multiple neuraminidases in avian HA VLPs is a promising approach for developing a universal influenza A vaccine against avian and human influenza virus infections.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Neuraminidase/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Vacinas de Partículas Semelhantes a Vírus/imunologia , Animais , Anticorpos Antivirais/imunologia , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neuraminidase/genética , Análise de Sobrevida , Vacinação , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética
19.
FASEB J ; 36(3): e22182, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35113455

RESUMO

Pre-pandemic influenza H5N1 vaccine has relatively low immunogenicity and often requires high antigen amounts and two immunizations to induce protective immunity. Incorporation of vaccine adjuvants is promising to stretch vaccine doses during pandemic outbreaks. This study presents a physical radiofrequency (RF) adjuvant (RFA) to conveniently and effectively increase the immunogenicity and efficacy of H5N1 vaccine without modification of vaccine preparation. Physical RFA is based on a brief RF treatment of the skin to induce thermal stress to enhance intradermal vaccine-induced immune responses with minimal local or systemic adverse reactions. We found that physical RFA could significantly increase H5N1 vaccine-induced hemagglutination inhibition antibody titers in murine models. Intradermal H5N1 vaccine in the presence of RFA but not vaccine alone significantly lowered lung viral titers, reduced body weight loss, and improved survival rates after lethal viral challenges. The improved protection in the presence of RFA was correlated with enhanced humoral and cellular immune responses to H5N1 vaccination in both male and female mice, indicating no gender difference of RFA effects in murine models. Our data support further development of the physical RFA to conveniently enhance the efficacy of H5N1 vaccine.


Assuntos
Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais/imunologia , Feminino , Testes de Inibição da Hemaglutinação/métodos , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pandemias/prevenção & controle , Vacinação/métodos
20.
PLoS One ; 17(2): e0255495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35148322

RESUMO

BACKGROUND: Vaccine hesitancy is increasing. We assessed attitudes toward influenza and COVID-19 vaccines and the relation between hesitancy to influenza vaccine and hesitancy towards COVID-19 vaccines. METHODS: A structured questionnaire administered during September 2020 to a representative sample of the Jewish Israeli population assessed attitudes and acceptance of influenza and COVID-19 vaccines. Factors for vaccine hesitancy were determined using logistic regression. Questionnaires were administered prior to the release of clinical data regarding efficacy and safety of COVID-19 vaccines and prior to vaccine rollout. RESULTS: We approached 10,625 people, of these 2,080 responded (19%), and 2,024 completed the questionnaire (97.3%), 64.9% aged 15-64 years and 35.1% aged ≥65 years. 37% had co-morbidities. 43.5% experienced financial deterioration due to the pandemic. 65.9% received influenza vaccine ≥1 time in the past. Influenza vaccination rates were higher in the elderly (81.8%). Reasons for influenza vaccine hesitancy were opinions that the vaccine is ineffective (27.1%), and fear of side effects (29.3%). 8.2% of people aged 16-64 and 13.8% of people aged≥65 refused to be vaccinated at least once over the course of one's lifetime. Percent of responders willing to receive a COVID-19 vaccine were higher than percent of responders willing to receive the influenza vaccine both in people aged 16-64 years (942 (72.3%) vs. 38.4%, respectively) and in people 65 years and older (84.0% vs. 76.8%, respectively). Hesitancy towards COVID-19 vaccine was associated with hesitancy towards other vaccines. Only 26.8% would participate in a COVID-19 vaccine trial. CONCLUSIONS: Willingness to receive COVID-19 vaccine was higher than willingness to receive influenza vaccine. The results point to areas of fear from influenza vaccines side effects and lack of knowledge regarding influenza vaccines effectiveness that can be addressed to increase acceptance. Hesitancy towards other vaccines was associated with hesitancy towards COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Influenza/imunologia , Judeus , Pandemias , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Estações do Ano , Inquéritos e Questionários , Adulto Jovem
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