scholarly journals Understanding Antibody Responses in Early Life: Baby Steps towards Developing an Effective Influenza Vaccine

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1392
Author(s):  
Elene A. Clemens ◽  
Martha A. Alexander-Miller
Keyword(s):  
Immune Responses ◽  
Specific Antibody ◽  
Young Infant ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Respiratory Pathogens ◽  
Young Infants ◽  
Recent Developments ◽  
Substantial Interest

The immune system of young infants is both quantitatively and qualitatively distinct from that of adults, with diminished responsiveness leaving these individuals vulnerable to infection. Because of this, young infants suffer increased morbidity and mortality from respiratory pathogens such as influenza viruses. The impaired generation of robust and persistent antibody responses in these individuals makes overcoming this increased vulnerability through vaccination challenging. Because of this, an effective vaccine against influenza viruses in infants under 6 months is not available. Furthermore, vaccination against influenza viruses is challenging even in adults due to the high antigenic variability across viral strains, allowing immune evasion even after induction of robust immune responses. This has led to substantial interest in understanding how specific antibody responses are formed to variable and conserved components of influenza viruses, as immune responses tend to strongly favor recognition of variable epitopes. Elicitation of broadly protective antibody in young infants, therefore, requires that both the unique characteristics of young infant immunity as well as the antibody immunodominance present among epitopes be effectively addressed. Here, we review our current understanding of the antibody response in newborns and young infants and discuss recent developments in vaccination strategies that can modulate both magnitude and epitope specificity of IAV-specific antibody.

scholarly journals Development and validation of an assay for detection of Japanese Encephalitis virus specific antibody responses

2020 ◽  
Author(s):  
Pradeep Darshana Pushpakumara ◽  
Chandima Jeewandara ◽  
Laksiri Gomes ◽  
Yashodha Perera ◽  
Ananda Wijewickrama ◽  
...  
Keyword(s):  
Immune Responses ◽  
Japanese Encephalitis Virus ◽  
Disease Severity ◽  
Japanese Encephalitis ◽  
Specific Antibody ◽  
Encephalitis Virus ◽  
Antibody Responses ◽  
Specific Antibodies ◽  
Dengue Disease ◽  
Conserved Regions

AbstractBackgroundAlthough immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity.Methodology/Principal findings20 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N=30), those who were only immune to the JEV and not DENV (JEV+DENV-, N=30), those who were only immune to DENV(JEV-DENV+, N=30) and in those who were immune to both viruses (JEV+DENV+, N=30). 7/20 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV-and 30/30 JEV+DENV+individuals, and only 3/30 (10%) JEV-DENV+individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n=175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n=175) (OR 5.3, 95% CI 3.3 to 8.3).Conclusions/SignificanceAs our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.Author summaryBoth Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) co-circulate in the same geographical region and have a potential to modulate the immune responses to each other. However, due to the difficulty in identifying antibody responses specific to either virus due to the highly cross-reactive nature of virus-specific antibodies, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV-specific, DENV non cross-reactive antibody responses by identifying JEV-specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV-specific antibodies associates with dengue disease severity. 20 JEV-specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed. We found that seven peptides were highly immunogenic and specific to the JEV and we further evaluated the usefulness of an ELISA developed using these pools of peptides. We found that our in-house ELISA was found to be significantly more sensitive some of the existing commercial assays. As this assay appears to be highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.

scholarly journals A Replication-Defective Influenza Virus Harboring H5 and H7 Hemagglutinins Provides Protection against H5N1 and H7N9 Infection in Mice

2020 ◽  
Author(s):  
Xingui Tian ◽  
Shelby Landreth ◽  
Yao Lu ◽  
Kannupriya Pandey ◽  
Yan Zhou
Keyword(s):  
Avian Influenza ◽  
Immune Responses ◽  
Vaccine Candidate ◽  
Mortality Rates ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
H7n9 Virus ◽  
Complete Protection ◽  
Virus Challenge ◽  
Ha Gene

The recent highly pathogenic avian influenza (HPAI) H5N1 and H7N9 viruses have caused hundreds of human infections with high mortality rates. Although H5N1 and H7N9 viruses have been mainly limited to avian species, there is high potential for these viruses to acquire human-to-human transmission and initiate a pandemic. A highly safe and effective vaccine is needed to protect against a potential H5N1 or H7N9 influenza pandemic. Here, we report the generation and evaluation of two reassortant influenza viruses, PR8-H5-H7NA and PR8-H7-H5NA. These viruses contain six internal segments from A/Puerto Rico/8/1934 (PR8), the HA segment from either A/Alberta/01/2014 (H5N1) [AB14 (H5N1)] or A/British Columbia/01/2015 (H7N9) [BC15 (H7N9)], and a chimeric NA segment with either the BC15 (H7N9) HA gene or the AB14 (H5N1) HA gene flanked by the NA packaging signals of PR8. These viruses expressed both H5 and H7 HAs in infected cells, replicated to high titres when exogenous NA was added to the culture medium in vitro, and were replication-defective and non-virulent when administered intranasally in mice. Moreover, intranasal vaccination with PR8-H5-H7NA elicited robust immune responses to both H5 and H7 viruses, conferring complete protection against both AB14 (H5N1) and BC15 (H7N9) challenges in mice. Conversely, vaccination with PR8-H7-H5NA only elicited robust immune responses towards the H7 virus, which conferred complete protection against BC15 (H7N9) but not against AB14 (H5N1) in mice. Therefore, PR8-H5-H7NA has strong potential to serve as a vaccine candidate against both H5 and H7 subtypes of influenza viruses. Importance Avian influenza H5N1 and H7N9 viruses infected human with high mortality rates. A highly safe and effective vaccine is needed to protect against a potential pandemic. We generated and evaluated two reassortant influenza viruses, PR8-H5-H7NA and PR8-H7-H5NA as vaccine candidates. Each virus contains one type of HA in segment 4 and the other subtype of HA in segment 6, thus expressing both H5 and H7 subtypes of HA molecule. The viruses’ replication is dependent in the addition of exogenous NA in cell culture, and are replication-defective in vivo. Vaccination of PR8-H5-H7NA virus confers protection to both H5N1 and H7N9 virus challenge; conversely, vaccination of PR8-H7-H5NA only provides protection to H7N9 virus challenge. Our data revealed when engineering such virus, the H5 or H7 HA in segment 6 affects the immunogenicity. PR8-H5-H7NA has strong potential to serve as a vaccine candidate against both H5 and H7 subtypes of influenza viruses.

scholarly journals DNA Immunization with Plasmids Encoding Fusion and Nucleocapsid Proteins of Bovine Respiratory Syncytial Virus Induces a Strong Cell-Mediated Immunity and Protects Calves against Challenge

2007 ◽  
Vol 81 (13) ◽  
pp. 6879-6889 ◽  
Author(s):  
Mathieu Boxus ◽  
Marylène Tignon ◽  
Stefan Roels ◽  
Jean-François Toussaint ◽  
Karl Walravens ◽  
...  
Keyword(s):  
Cellular Response ◽  
Clinical Signs ◽  
Effective Vaccine ◽  
Cell Mediated Immunity ◽  
Respiratory Pathogens ◽  
Lymphoproliferative Response ◽  
Promising Alternative ◽  
Young Infants ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial viruses (RSV) are one of the most important respiratory pathogens of humans and cattle, and there is currently no safe and effective vaccine prophylaxis. In this study, we designed two codon-optimized plasmids encoding the bovine RSV fusion (F) and nucleocapsid (N) proteins and assessed their immunogenicity in young calves. Two administrations of both plasmids elicited low antibody levels but primed a strong cell-mediated immunity characterized by lymphoproliferative response and gamma interferon production in vitro and in vivo. Interestingly, this strong cellular response drastically reduced viral replication, clinical signs, and pulmonary lesions after a highly virulent challenge. Moreover, calves that were further vaccinated with a killed-virus vaccine developed high levels of neutralizing antibody and were fully protected following challenge. These results indicate that DNA vaccination could be a promising alternative to the classical vaccines against RSV in cattle and could therefore open perspectives for vaccinating young infants.

Longitudinal and Functional Analysis of Spontaneous NY-ESO-1-Specific Antibody Responses in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2831-2831
Author(s):  
Sebastian Kobold ◽  
Yanran Cao ◽  
Sinje Tams ◽  
Britta Marlen Bartels ◽  
Tim Lütkens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Specific Antibodies ◽  
Functional Capabilities ◽  
Bone Marrow Plasma ◽  
Ct Antigen ◽  
Antibody Titers

Abstract Abstract 2831 Poster Board II-807 Its tumor-restricted expression and its high immunogenicity render cancer-testis (CT) antigen NY-ESO-1 an exquisite target for antigen-specific immunotherapies. Spontaneous antibody responses against NY-ESO-1 are typically found in a subset of patients with solid tumors. However, little is known regarding serological immune responses against NY-ESO-1 in patients with hematological malignancies including multiple myeloma (MM). Furthermore, no consequent longitudinal analyses have been performed correlating NY-ESO-1-specific antibody titers with the clinical development of the given malignancy. Finally, nothing is known regarding the functional capabilities of spontaneously occurring anti-NY-ESO-1 antibodies in MM or other malignancies. Here, we performed the first longitudinal and functional investigation of NY-ESO-1-specific antibody responses in MM analyzing 1100 sera and 200 bone marrow plasma samples of 194 MM patients. Sera and BM plasma samples of 100 healthy donors served as controls. Screening sera and bone marrow plasma of our MM patients by Enzyme-linked Immunosorbent Assay (ELISA) using full length recombinant NY-ESO-1 protein, we found that 5/194 patients had high-titered antibody responses against this CT antigen. A quantitative B cell ELISPOT demonstrated NY-ESO-1-specific B cells in the peripheral blood as well as in the bone marrow of the respective MM patients. In a western blot analysis, spontaneous NY-ESO-1-specific immune responses in the patients were found to be highly specific for both native and recombinant protein. Epitope mapping in an ELISA using 18 overlapping NY-ESO-1 20mer peptides showed that antibody responses were restricted to the first 70 amino acids of the full-length protein. NY-ESO-1-specific antibodies consisted mainly of IgG1 and to a lower extent of IgG3 subtypes. No IgG2, IgG4, IgM or IgA antibodies against NY-ESO-1 were detected. Interestingly, antibody affinity increased over the course of the disease suggesting an affinity driven antibody maturation. Accordingly, NY-ESO-1-specific antibodies of MM patients were found to be potent complement activators in a western blot technique. On the other hand, despite the high functional capabilities of NY-ESO-1-specific antibodies, antibody titers increased with each NY-ESO-1-expressing (as indicated by reverse-transcriptase-polymerase-chain-reaction and immunohistochemistry) recurrence of the disease. In conclusion, we demonstrate here the spontaneous occurrence of high-titered NY-ESO-1-specific antibodies in MM patients. One reason for the relatively low frequency of antibody responses against NY-ESO-1 might be that most patients were in early stages of the disease or in remission at the time the analysis was performed. Antibodies were produced by NY-ESO-1-specific B cells detectable in the bone marrow as well as in the peripheral blood of the patients. NY-ESO-1-specific antibodies were evoked by a distinct and immunodominant fragment of NY-ESO-1. Affinity maturation of this response and complement activation by the spontaneously occurring NY-ESO-1-specific IgG1-type antibodies speak in favour of an effective serological immune response. However, positive correlation of antibody titers with tumor burden and recurrence of the disease suggest an inability of antibodies targeting intracellular protein NY-ESO-1 to control the course of the disease, at least in the long run. Antigen-specific immunotherapy might be necessary to shape NY-ESO-1-specific immunity in MM patients and, particularly, to mobilize tumor-specific T cell responses. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immune Failure in the Absence of Profound CD4+ T-Lymphocyte Depletion in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques

2004 ◽  
Vol 78 (1) ◽  
pp. 275-284 ◽  
Author(s):  
Vanessa M. Hirsch ◽  
Sampa Santra ◽  
Simoy Goldstein ◽  
Ronald Plishka ◽  
Alicia Buckler-White ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Specific Antibody ◽  
Hepatitis A Virus ◽  
Antibody Responses ◽  
Lymphoid Tissues ◽  
Humoral Immune ◽  
Immunodeficiency Virus ◽  
Immune Defect

ABSTRACT A fraction of simian immunodeficiency virus (SIV)-infected macaques develop rapidly progressive disease in the apparent absence of detectable SIV-specific antibody responses. To characterize the immunopathogenesis of this syndrome, we studied viral load, CD4+ T-lymphocyte numbers as well as cellular and humoral immune responses to SIV and other exogenous antigens in four SIVsm-infected rhesus macaques that progressed to AIDS 9 to 16 weeks postinoculation. Each of these animals exhibited high levels of viremia but showed relatively preserved CD4 T lymphocytes in blood and lymphoid tissues at the time of death. Transient SIV-specific antibody responses and cytotoxic T-lymphocyte responses were observed at 2 to 4 weeks postinoculation. Two of the macaques that were immunized sequentially with tetanus toxoid and hepatitis A virus failed to develop antibody to either antigen. These studies show that the SIV-infected rapid progressor macaques initially mounted an appropriate but transient cellular and humoral immune response. The subsequent immune defect in these animals appeared to be global, affecting both cellular and humoral immunity to SIV as well as immune responses against unrelated antigens. The lack of CD4 depletion and loss of humoral and cellular immune responses suggest that their immune defect may be due to an early loss in T helper function.

scholarly journals Defective SARS-CoV-2 immune responses in an immunocompromised individual with prolonged viral replication

2021 ◽  
Author(s):  
Claire L Gordon ◽  
Olivia C Smibert ◽  
Natasha E Holmes ◽  
Kyra Y L Chua ◽  
Rose Morgan ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Responses ◽  
Viral Replication ◽  
Specific Antibody ◽  
Late Onset ◽  
Antibody Responses ◽  
Hla Dr ◽  
Immunocompromised Individual ◽  
Immunocompromised Hosts

Abstract We describe SARS-CoV-2-specific immune responses in a patient with lymphoma and recent PD-1 inhibitor therapy with late onset of severe COVID-19 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR +/CD38 +-activation, IL-6 and IL-18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2-specific antibody responses were absent and SARS-CoV-2 specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

scholarly journals Impaired Cellular Immunity to SARS-CoV-2 in Severe COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling Ni ◽  
Meng-Li Cheng ◽  
Yu Feng ◽  
Hui Zhao ◽  
Jingyuan Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Specific Antibody ◽  
Peripheral Blood ◽  
Neutralizing Antibodies ◽  
Acute Infection ◽  
Peripheral Blood Lymphocytes ◽  
Antibody Responses ◽  
Humoral Immune

The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, with decreased IFNγ expression in CD4+ T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.

scholarly journals Adjuvant-Dependent Enhancement of HIV Env-Specific Antibody Responses in Infant Rhesus Macaques

2018 ◽  
Vol 92 (20) ◽  
Author(s):  
Bonnie Phillips ◽  
Koen K. A. Van Rompay ◽  
Jennifer Rodriguez-Nieves ◽  
Clarisse Lorin ◽  
Marguerite Koutsoukos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Specific Antibody ◽  
Hiv Transmission ◽  
Rhesus Macaques ◽  
Pediatric Population ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Macaque Model ◽  
Pediatric Vaccines

ABSTRACTToward the goal of developing an effective HIV vaccine that can be administered in infancy to protect against postnatal and lifelong sexual HIV transmission risks, the current pilot study was designed to compare the effect of novel adjuvants on the induction of HIV Env-specific antibody responses in infant macaques. Aligning our studies with the adjuvanted proteins evaluated in a prime-boost schedule with ALVAC in the ongoing HVTN (HIV Vaccine Trials Network) 702 efficacy trial, we selected the bivalent clade C Env immunogens gp120 C.1086 and gp120 TV1 in combination with the MF59 adjuvant. However, we hypothesized that the adjuvant system AS01, that is included in the pediatric RTS,S malaria vaccine, would promote Env-specific antibody responses superior to those of the oil-in-water MF59 emulsion adjuvant. In a second study arm, we compared two emulsions, glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) and 3M-052-SE, containing Toll-like receptor 4 (TLR4) and TLR7/TLR8 (TLR7/8) ligand, respectively. The latter adjuvant had been previously demonstrated to be especially effective in activating neonatal antigen-presenting cells. Our results demonstrate that different adjuvants drive quantitatively or qualitatively distinct responses to the bivalent Env vaccine. AS01 induced higher Env-specific plasma IgG antibody levels than the antigen in MF59 and promoted improved antibody function in infants, and 3M-052-SE outperformed GLA-SE by inducing the highest breadth and functionality of antibody responses. Thus, distinct adjuvants are likely to be required for maximizing vaccine-elicited immune responses in infants, particularly when immunization in infancy aims to elicit both perinatal and lifelong immunity against challenging pathogens such as HIV.IMPORTANCEAlum remains the adjuvant of choice for pediatric vaccines. Yet the distinct nature of the developing immune system in infants likely requires novel adjuvants targeted specifically at the pediatric population to reach maximal vaccine efficacy with an acceptable safety profile. The current study supports the idea that additional adjuvants for pediatric vaccines should be, and need to be, tested in infants for their potential to enhance immune responses. Using an infant macaque model, our results suggest that both AS01 and 3M-052-SE can significantly improve and better sustain HIV Env-specific antibody responses than alum. Despite the limited number of animals, the results revealed interesting differences that warrant further testing of promising novel adjuvant candidates in larger preclinical and clinical studies to define the mechanisms leading to adjuvant-improved antibody responses and to identify targets for adjuvant and vaccine optimization.

scholarly journals A Strategy to Elicit M2e-Specific Antibodies Using a Recombinant H7N9 Live Attenuated Influenza Vaccine Expressing Multiple M2e Tandem Repeats

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 133
Author(s):  
Daria Mezhenskaya ◽  
Irina Isakova-Sivak ◽  
Tatiana Kotomina ◽  
Victoria Matyushenko ◽  
Min-Chul Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Tandem Repeats ◽  
Phase 1 ◽  
Public Health Problem ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Passive Protection ◽  
Live Attenuated Influenza Vaccine

Influenza viruses remain a serious public health problem. Vaccination is the most effective way to prevent the disease; however, seasonal influenza vaccines demonstrate low or no effectiveness against antigenically drifted and newly emerged influenza viruses. Different strategies of eliciting immune responses against conserved parts of various influenza virus proteins are being developed worldwide. We constructed a universal live attenuated influenza vaccine (LAIV) candidate with enhanced breadth of protection by modifying H7N9 LAIV by incorporating four epitopes of M2 protein extracellular part into its hemagglutinin molecule. The new recombinant H7N9+4M2e vaccine induced anti-M2e antibody responses and demonstrated increased protection against heterosubtypic challenge viruses in direct and serum passive protection studies, compared to the classical H7N9 LAIV. The results of our study suggest that the H7N9+4M2e warrants further investigation in pre-clinical and phase 1 clinical trials.

scholarly journals The Effects of Birth Year, Age and Sex on Hemagglutination Inhibition Antibody Responses to Influenza Vaccination

2018 ◽  
Author(s):  
Ewan P. Plant ◽  
Angelia A Eick-Cost ◽  
Hussein Ezzeldin ◽  
Jose L Sanchez ◽  
Zhiping Ye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccination ◽  
Military Personnel ◽  
Hemagglutination Inhibition ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Birth Cohorts ◽  
Vaccine Responses ◽  
Inhibition Antibody ◽  
Influenza Activity

The first exposure to influenza is thought to impact subsequent immune responses later in life. The consequences of this can be seen during influenza epidemics and pandemics with differences in morbidity and mortality for different birth cohorts. With the development of new universal vaccines there is need for better understanding of how vaccine responses are affected by early exposures to influenza viruses. In this analysis of hemagglutination inhibition (HI) antibody responses in two cohorts of military personnel we noticed differences related to birth year. These data suggest that HI antibody production, in response to influenza vaccination, is affected by influenza activity in the years following birth. The magnitude of this antibody response is associated with, among other factors, the influenza strain that circulated following birth.

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