H1N1 Vaccine Research Articles

Physical radiofrequency adjuvant enhances immune responses to influenza H5N1 vaccination.

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.

A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination.

Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45HA2 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45HA2, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies.

Seasonal and 2009 Pandemic H1N1 Vaccine Acceptance as a Predictor for COVID-19 Vaccine Acceptance.

The emergence of COVID-19 also began an unprecedented production and distribution of several novel COVID-19 vaccines to combat the pandemic. Unfortunately, with the history of vaccine hesitancy in the United States and abroad, concern remains regarding the ability to vaccinate enough of the population to achieve herd immunity. In this study, 101 adults were surveyed about their vaccine experience in the waiting room of their visit to a Med-Peds clinic in Albany County, NY, to gauge interest in the upcoming rollout of COVID-19 vaccines. Questions included their opinions on seasonal influenza vaccines, the 2009 H1N1 vaccine, and the COVID-19 vaccine. The results of our survey are consistent with previous studies where gaps in acceptance were notable in black populations, lower education, and individuals with public health insurance. Furthermore, 92.9% of respondents who denied getting the 2009 H1N1 pandemic vaccine also did not plan to receive the COVID-19 vaccine (p<0.05), therefore a strong correlation was found between receipt of the previous 2009 H1N1 pandemic vaccine and the COVID-19 vaccine acceptance. The qualitative results of our study revealed that COVID-19 precautions deterred people from receiving the seasonal influenza vaccine, and a lack of information on the COVID-19 vaccine caused hesitancy to receive the vaccine on behalf of patients.

Selection of an Optimal Recombinant Egyptian H9N2 Avian Influenza Vaccine Strain for Poultry with High Antigenicity and Safety.

For the development of an optimized Egyptian H9N2 vaccine candidate virus for poultry, various recombinant Egyptian H9N2 viruses generated by a PR8-based reverse genetics system were compared in terms of their productivity and biosafety since Egyptian H9N2 avian influenza viruses already possess mammalian pathogenicity-related mutations in the hemagglutinin (HA), neuraminidase (NA), and PB2 genes. The Egyptian HA and NA genes were more compatible with PR8 than with H9N2 AIV (01310) internal genes, and the 01310-derived recombinant H9N2 strains acquired the L226Q reverse mutation in HA after passages in eggs. Additionally, the introduction of a strong promoter at the 3′-ends of PB2 and PB1 genes induced an additional mutation of P221S. When recombinant Egyptian H9N2 viruses with intact or reverse mutated HA (L226Q and P221S) and NA (prototypic 2SBS) were compared, the virus with HA and NA mutations had high productivity in ECES but was lower in antigenicity when used as an inactivated vaccine due to its high binding affinity into non-specific inhibitors in eggs. Finally, we substituted the PB2 gene of PR8 with 01310 to remove the replication ability in mammalian hosts and successfully generated the best recombinant vaccine candidate in terms of immunogenicity, antigenicity, and biosafety.

The antigenicity of SARS-CoV-2 Delta variants aggregated 10 high-frequency mutations in RBD has not changed sufficiently to replace the current vaccine strain

Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.

Immune Enhancement by the Tetra-Peptide Hydrogel as a Promising Adjuvant for an H7N9 Vaccine against Highly Pathogenic H7N9 Virus.

Background: Short peptide hydrogel was reported as a possible adjuvant for vaccines. In order to evaluate whether the Tetra-Peptide Hydrogel can be a promising adjuvant for an H7N9 vaccine against the highly pathogenic H7N9 virus, we conducted this study. Methods: Tetra-Peptide Hydrogels (D and L conformations) were prepared by a self-assembly system using a Naproxen acid modified tetra peptide of GFFY (Npx-GFFY). Mice received two immunizations with the D-Tetra-Peptide Hydrogel adjuvant vaccine, the L-Tetra-Peptide Hydrogel adjuvant vaccine, or the split vaccine. Fourteen days following the second dose, the mice were challenged with the highly pathogenic A/Guangdong/GZ8H002/2017(H7N9) virus. The mice were observed for signs of illness, weight loss, pathological alterations of the lung tissues and immune responses in the following 2 weeks. Results: The D/L-Tetra-Peptide Hydrogels resembled long bars with hinges on each other, with a diameter of ~10 nm. The H7N9 vaccine was observed to adhere to the hydrogel. All the unvaccinated mice were dead by 8 days post infection with H7N9. The mice immunized by the split H7N9 vaccine were protected against infection with H7N9. Mice immunized by D/L-Tetra-Peptide Hydrogel adjuvant vaccines experienced shorter symptomatic periods and their micro-neutralization titers were higher than in the split H7N9 vaccine at 2 weeks post infection. The hemagglutinating inhibition (HI) titer in the L-Tetra-Peptide Hydrogel adjuvant vaccine group was higher than that in the split H7N9 vaccine 1 week and 2 weeks post infection. The HI titer in the D-Tetra-Peptide Hydrogel adjuvant vaccine group was higher than that in the split H7N9 vaccine at 2 weeks post infection. Conclusion: The D/L Tetra-Peptide Hydrogels increased the protection of the H7N9 vaccine and could be promising adjuvants for H7N9 vaccines against highly pathogenic H7N9 virus.

Benefit-cost analysis of a H7N9 vaccination program in poultry in Guangxi, China

China launched a H7N9 vaccination program in poultry, starting from the Guangxi and Guangdong provinces in July 2017, followed by other provinces in September 2017, as a response to a steep increase of H7N9 influenza human infections from September 2016. Since then, H5-H7 bivalent vaccine has been used in the nationwide avian influenza compulsory vaccination program to replace the existing H5N1 vaccine. However, the economic returns of the H7N9 vaccination program in China have never been adequately assessed. This study was designed to evaluate the economic value of the H7N9 vaccination program in Guangxi by assessing the benefits and costs of the program compared to not vaccinating against H7N9.A benefit-cost analysis (BCA) was undertaken to evaluate the adoption of a vaccination program against H7N9 in each of three consecutive years from July 2017 to June 2020 with the baseline scenario (the absence of H7N9 vaccination in the 12-month period July 2016 to June 2017). Both animal and public health perspectives were included in the BCA framework and took account of both the private and public sectors.Benefit-Cost Ratio (BCR) of the three-year H7N9 vaccination program was 18.6 (90 %PI: 15.4; 21.8), and total Net Present Values reached to CNY 1.63 billion (90 %PI: 1.37 billion; 1.89 billion). The extra revenue generated by the yellow broiler industry comprised 93.8 % of the total benefits after adoption of H7N9 vaccination program in Guangxi. While cost-savings in public health and animal health expenditure avoided were 3.6 % and 2.6 %, respectively. Total costs arising from adoption of the revised vaccination program over the three years were CNY 12.46 million (90 %PI: 11.49 million; 14.14 million), CNY 34.87 million (90 %PI: 31.88 million; 40.06 million), and CNY 44.28 million (90 %PI: 39.66 million; 52.27 million), respectively. Sensitivity analysis found the yellow broiler wholesale prices contributed 97.7 % of the variance of the total NPV of three vaccination years. The study results demonstrate the significant economic advantage of implementing a vaccination program against H7N9 in Guangxi. It also offers a new set of evidence to China’s H7N9 vaccination policy and debates around economic values of conducting routine avian influenza vaccination.

USING MRNA VACCINES TO ENDANGER POPULATION IS A RECURRENT HUMANITY DISASTER

When this article is submitted for reprint, at least 252,400,057 people or 76% of the population in the U.S. have received at least one dose of mRNA vaccines. I started predicting the dangers of mRNA vaccines before March 2021 and update my article periodically. My prior model study enabled me to identify many flaws in the foundation of medicine, and I also considered consistent failure in predicting drug side effects in the past and systematic failure of FDA in keeping out dangerous drugs such as Diethylstilbestrol (DES) and swine flu vaccine from the market. By studying mRNA expression dynamics and kinetics, I predicted that mRNA vaccines may adversely affect brain, all vital organs, cancer growth, human genome integrity, viral evolution, pre-existing chronic diseases, fetus development, etc. I found the number of deaths caused by mRNA vaccines was grossly underestimated, and that 95% effectiveness rate and 90% death rate reduction are meaningless and misleading. Now, case reports on liver damages start appearing. I urge societies to question disease risk theory. If a drug can harm one or more persons in a specific way by nonaccident, this same harm must happen to all others who have exposed to the drug. The concealment of drug injuries can be attributed to human massive organ reserves, the interference effects of thousands of life factors, expected lags in damages realization, the use of symptom-based method, etc. After those flaws are corrected, anyone should see the brutal reality that the same harm must happen to all exposed persons. In this reprinted article, I urge governments and societies to sponsor studies to understand how mRNA vaccines damage liver and brain, what could be done to mitigate future adverse impacts and how to prevent humanity disasters like this from happening again.

The effectiveness of H9N2 vaccination in commercial broilers flocks under natural field infection

The effectiveness of H9N2 vaccination in commercial broilers flocks under natural field infection

The effectiveness of H9N2 vaccination in commercial broilers flocks under natural field infection

The effectiveness of H9N2 vaccination in commercial broilers flocks under natural field infection

The effectiveness of H9N2 vaccination in commercial broilers flocks under natural field infection

The effectiveness of H9N2 vaccination in commercial broilers flocks under natural field infection

The residual H5N1 antibody results and epidemiological characteristics involved on the volunteer group in Ninh Hoa distric

Non-controlled longitudinal study were carry on 185 subjects who received 2 doses of 15µg IVACFLU-A / H5N1 vaccine 21 days apart to determine persistent of antibody-H5N1 and some Epidemiological characteristics involved, the results showed that: 18 months after IVACFLU-A / H5N1 vaccination, the rate of antibody protection (titre ≥ 1/40) still reached 61.6%; GMTs of the injection group reached 49.2. No statically differences on age, gender and epidemiological characteristics related persistent of anti-H5N1 antibody after vaccination. The research is still ongoing until 36 months after vaccination.

Finnish children who experienced narcolepsy after receiving the Pandemrix vaccine during the 2009-2010 H1N1 pandemic demonstrated high level of psychosocial problems.

We assessed psychosocial burdens in children who developed narcolepsy after receiving the Pandemrix H1N1 vaccine during the 2009-2010 pandemic. Parental quality of life was also assessed. This multicentre study covered four of the five Finnish University Hospital Districts, which dealt with about 90% of the paediatric narcolepsy cases after the Pandemrix vaccination. The medical records of children diagnosed from 2010 to 2014 were reviewed. The questionnaires included the Youth Self-Report (YSR), Children's Depression Inventory (CDI), the Child Behaviour Checklist (CBCL) and questions on parental resources, stress and quality of life. We obtained the medical records of 94 children who were aged 5-17years at the time of their narcolepsy diagnosis and questionnaire data for 73 of those children. Most children had strong narcolepsy symptoms, and 25% had CDI scores that suggested depression. In addition, 41% had total CBCL problem scores above the clinically significant limit and 48% were anxious, withdrawn and had somatic complaints. Sleep latency was weakly associated with the CBCL total problem score. Half of the children needed psychiatric interventions and parental stress was common. Depression and behavioural problems were common in children with narcolepsy after the Pandemrix vaccination and their parents frequently reported feeling stressed.

Carboxymethyl chitosan bounded iron oxide nanoparticles and gamma-irradiated avian influenza subtype H9N2 vaccine to development of immunity on mouse and chicken.

BackgroundAvian influenza virus (AIV) subtype H9N2 is a low pathogenic avian influenza virus (LPAIV).ObjectiveThis study aims to evaluate the humoral and cellular immunity in vaccinated mice and broiler chicken by irradiated AIV antigen plus carboxymethyl chitosan bounded iron oxide nanoparticles (CMC‐IO NPs) as an adjuvant.MethodsAIV subtype H9N2 with 108.5 EID50/ml and haemagglutinin antigen assay about 10 log2 was irradiated by 30 kGy gamma radiation dose. Then, the gamma‐irradiated AIV was used as an inactivated vaccine and conjugated with CMC‐IO NPs to improve immune responses on mice. IO NPs must be applied in all activated tests using 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC) and N‐hydroxysulfosuccinimide sodium salt (sulfo‐NHS), and then functionalized by CMC as IO‐CMC. Fourier transform infrared (FTIR) spectra on functionalized IO‐CMC showed a peak of 638 cm−1 which is a band between metal and O (Fe‐O).ResultsBased on the comparison between the two X‐ray diffraction (XRD) patterns on Fe2O3‐NPs and IO‐CMC, the characteristics of IO‐NPs did not change after carboxymethylation. A CHN Analyzer was applied to measure the molecular weight of IO‐CMC that was calculated as 1045 g. IO‐CMC, irradiated AIV‐IO‐CMC and formalin AIV‐IO‐CMC were injected into 42 BALB/c mice in six groups. The fourth group was the negative control, and the fifth and sixth groups were inoculated by irradiated AIV‐ISA70 and formalin AIV‐ISA70 vaccines. An increase in haemagglutination inhibition (HI) antibody titration was observed in the irradiated AIV‐IO‐CMC and formalin AIV‐IO‐CMC groups (p < 0.05). In addition, increases in the lymphoproliferative activity of re‐stimulated splenic lymphocytes, interfron‐γ (IFN‐γ) and interleukin‐2 (IL‐2) concentration in the irradiated AIV‐IO‐CMC group demonstrated the activation of Type 1 helper cells. The concentration of IL‐4 was without any significant increases in non‐group.ConclusionsAccordingly, Th2 activation represented no increase. Finally, the finding showed that AIV‐IO‐CMC was effective on enhancing immunogenicity as irradiated AIV antigen administered with a clinically acceptable adjuvant (i.e. IO‐CMC).

Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model

H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.

An introduction of the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) Project

The vaccine benefit-risk assessment entails comprehensive and systematic evaluation of the major benefits and risks of vaccine based on information after a marketing authorization. In 2009, the influenza A (H1N1) pandemic led to the licensing of new H1N1 vaccines in many countries including Europe. The post-marketing evaluation and monitoring of H1N1 vaccines was carried out based on a project previously conducted in Europe. In 2013, the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) project was launched with the support of Innovative Medicines Initiative (IMI) to address the limitations reported in the previous project. ADVANCE consisted of seven Work Packages (WPs), each indicating the vaccine benefitrisk monitoring readiness across four areas: Governance, Data source, &amp;#x0004d;ethods, and Study. First, a model for vaccine surveillance and governance with various functions such as decision making, quality management, execution, and financial administration was established. Also, the project developed a tool to identify, collect, and link the data sources available for vaccine surveillance. In addition, various methodologies were reviewed to assess the infectious disease burden, vaccine coverage, and benefit-risk based on linked data sources in Europe. Guidelines were proposed for real-world vaccine surveillance studies. Accordingly, a variety of tools and programs were developed, including a code of conduct related to the benefit-risk assessment of vaccines, ADVANCE International Research Readiness (AIRR), CodeMapper, and VaccO. Since the end of the ADVANCE project in 2019, the Vaccine Monitoring Collaboration for Europe (VAC4EU) has been conducting effective and sustainable vaccine benefit-risk monitoring programs based on the vision and ideology of ADVANCE. This study explains the contents and findings of ADVANCE with emphasis on WPs and proposes directions for establishing a vaccine benefit-risk assessment system in Korea.

Selenium nanoparticles enhance the efficacy of homologous vaccine against the highly pathogenic avian influenza H5N1 virus in chickens

A proper vaccination against avian influenza viruses in chicken can significantly reduce the risk of human infection. Egypt has the highest number of recorded humans highly pathogenic avian influenza (HPAI)-H5N1 infections worldwide despite the widespread use of homologous vaccines in poultry. Enhancing H5N1 vaccine efficacy is ultimately required to better control HPAI-H5N1. The aim of this study is to boost chicken immunity by combined with inactivated HPAI-H5N1 with selenium nanoparticles (SeNPs). The chickens groups 1–3 were fed diets supplemented with SeNPs concentrations (0.25, 0.5, and 1 mg/kg) for 3 weeks and then vaccinated (inactivated HPAI-H5N1). while groups 4,5 and 6 were fed with SeNPs free diets and administered with 0.5 ml of the vaccine combined with 0.02, 0.06, and 0.1 mg/dose of SeNPs and then all groups were challenged with homologous virus 3 weeks post-vaccination (WPV). Group 7, 8 were used as control positive and negative respectively. At 4, 5, and 6 WPV, antibody titer was considerably higher in the group fed a meal supplemented with 1 mg SeNPs/kg. In contrast, both methods of SeNPs supplementation significantly increased the Interleukin 2 (IL2), Interleukin 6 (IL6), and Interferon γ (IFNγ) expressions in the blood cells in a dose-dependent manner, with a higher expression observed in the group that was vaccinated with 0.1 mg/dose. After the challenge, all groups that received SeNPs via diet or vaccines dose showed significant reduction in viral shedding and milder inflammation in lung, trachea, spleen, and liver in addition to higher expression of IL2, IL6, and IFNγ, with the highest expression observed in the group that was vaccinated with 0.1 mg/dose compared the plain vaccinated group. The groups of 1 mg SeNPs/kg and combined vaccinated with 0.1 mg/dose showed the best vaccine efficacy. However, the group vaccinated with 0.1 mg/dose showed the earliest reduction in viral shedding. Overall, SeNPs supplementation in the diet and the administration of the vaccine formula with SeNPs could enhance vaccine efficacy and provide better protection against HPAI-H5N1 in chickens by enhancing cellular immunity and reducing inflammation. We recommend using SeNPs as a vaccine combination or feeding with diet to increase the immunity and vaccine efficacy against H5N1.

Identifying COVID-19 and H1N1 vaccination hesitancy or refusal among health care providers across North America, the United Kingdom, Europe, and Australia: a scoping review protocol.

ABSTRACTObjective:The aim of this scoping review is to describe and map the evidence on COVID-19 and H1N1 vaccination hesitancy or refusal among physicians, nurses, and pharmacists across North America, the United Kingdom, Europe, and Australia.Introduction:When global pandemics occur, including the coronavirus (COVID-19) pandemic, which originated in 2020, and the swine flu influenza pandemic (H1N1) of 2009, there is increased pressure for pharmaceutical companies and government agencies to develop safe and effective vaccines against these highly contagious illnesses. Following development and approvals, it then becomes essential that priority populations, including frontline health care providers, opt to receive these vaccinations to prevent illness and potential transmission to their patients. However, vaccine hesitancy or refusal has played a significant role in suboptimal vaccination rates globally. As health care providers, including physicians, nurses, and pharmacists, often administer vaccines, their vaccination views and behaviors are of great importance because they can directly affect the vaccination decisions of their patients.Inclusion criteria:The review will identify factors affecting COVID-19 and H1N1 vaccine hesitancy or refusal among physicians, nurses, and pharmacists across a range of countries. Published and unpublished evidence, including quantitative, qualitative, mixed methods research, and gray literature, will be eligible for inclusion.Methods:This scoping review protocol will follow JBI methodology. The search strategy will be developed with support from a health sciences librarian scientist to identify relevant evidence. Screening and data extraction will be conducted by two reviewers, with findings summarized and presented through narrative descriptions, tables, and figures.

AddaVax Formulated with PolyI:C as a Potential Adjuvant of MDCK-based Influenza Vaccine Enhances Local, Cellular, and Antibody Protective Immune Response in Mice

Poor immune responses to inactivated influenza vaccine can be improved by effective and safe adjuvants to increase antibody titers and cellular protective response. In our study, AddaVax and PolyI:C combined adjuvant (AP adjuvant) were used for influenza vaccine development. After immunizing BALB/c mice and Wistar rats intramuscularly, Split inactivated H3N2 vaccine adjuvanted with AP elicited higher serum hemagglutination-inhibition antibodies and IgG titers. We demonstrated that AP induced a transient innate immune cytokines production at the injection site, induced H3N2 uptake by DCs, increased recruitment of monocytes and DCs in LNs, and promoted H3N2 vaccine migration; AP facilitated vaccines to induce a vigorous adaptive immune response. Besides, AP showed good safety as shown by lymph nodes (LNs) size, spleens index of BALB/c mice, and weight changes and C-reaction protein level of BALB/c mice and Wistar rats after repeated administration of high-dose vaccine with or without adjuvant. These findings indicate that AP is a potential novel adjuvant and can be used as a safe and effective adjuvant for MDCK-based influenza inactivated vaccine to induce cellular and antibody protective response.

Temporal dynamics of persistent germinal centers and memory B cell differentiation following respiratory virus infection.

SummaryFollowing infection or immunization, memory B cells (MBCs) and long-lived plasma cells provide humoral immunity that can last for decades. Most principles of MBC biology have been determined with hapten-protein carrier models or fluorescent protein immunizations. Here, we examine the temporal dynamics of the germinal center (GC) B cell and MBC response following mouse influenza A virus infection. We find that antiviral B cell responses within the lung-draining mediastinal lymph node (mLN) and the spleen are distinct in regard to duration, enrichment for antigen-binding cells, and class switching dynamics. While splenic GCs dissolve after 6 weeks post-infection, mLN hemagglutinin-specific (HA+) GCs can persist for 22 weeks. Persistent GCs continuously differentiate MBCs, with “peak” and “late” GCs contributing equal numbers of HA+ MBCs to the long-lived compartment. Our findings highlight critical aspects of persistent GC responses and MBC differentiation following respiratory virus infection with direct implications for developing effective vaccination strategies.