Studies on antibody responses following neonatal immunization with influenza hemagglutinin DNA or protein
UMass Chan AffiliationsDepartment of Pathology
Program in Immunology and Virology
Graduate School of Biomedical Sciences
KeywordsAge Factors; Animals; Animals, Newborn; Antibodies, Viral; Disease Models, Animal; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Immunoglobulin G; Influenza A virus; Influenza Vaccines; Influenza, Human; Mice; Mice, Inbred BALB C; Th1 Cells; Th2 Cells; Vaccination; Vaccines, DNA; Vaccines, Synthetic
Medicine and Health Sciences
MetadataShow full item record
AbstractNeonatal mice have immature immune systems with defects in several components of inflammatory, innate, and specific immune responses and develop a preferential T helper type 2 response following immunization with many vaccine antigens. These studies were undertaken to determine whether 1-day-old neonatal mice immunized with plasmid DNA expressing influenza A/PR/8/34 hemagglutinin (H1) by either intramuscular (im) or gene gun (gg) inoculation were capable of generating humoral responses comparable to those in mice immunized as adults. The newborn mice developed stable, long-lived, protective anti-H1-specific IgG responses similar in titer to those of adult DNA-immunized mice. However, unlike the adult im and gg DNA immunizations, which develop polarized IgG2a and IgG1 responses, respectively, mice immunized as neonates developed a variety of IgG1, IgG2a, and mixed IgG1/IgG2a responses regardless of the inoculation method. Boosting increased but did not change these antibody profiles. In contrast to the DNA immunizations, inoculations of newborn mice with an A/PR/8/34 viral protein subunit preparation failed to elicit an antibody response. Temporal studies revealed that both responsiveness to protein vaccination and development of polarized patterns of T help following DNA immunization appeared by 2 weeks of age.
SourceVirology. 1999 May 10;257(2):406-14. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34334
Related ResourcesLink to article in PubMed
Showing items related by title, author, creator and subject.
Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A virusesHarshbarger, Wayne D.; Deming, Derrick; Lockbaum, Gordon J.; Attatippaholkun, Nattapol; Kamkaew, Maliwan; Hou, Shurong; Somasundaran, Mohan; Wang, Jennifer P.; Finberg, Robert W.; Zhu, Quan Karen; et al. (2021-01-25)Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.
The Role of Late Antigen in CD4 Memory T Cell Formation during Influena [i.e. Influenza] Infection: A DissertationBautista, Bianca L. (2016-10-18)While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late Ag in promoting CD4 memory T cell formation. In the experiments presented in this thesis, I demonstrate that late Ag is required to rescue responding CD4 T cells from default apoptosis and to program the transition to long-lived memory. Responding cells that failed to re-encounter Ag had decreased memory marker expression and failed to produce multiple cytokines upon re-stimulation. Ag recognition is required at a defined stage, as short-term Ag presentation provided 6 days after infection is able to restore canonical memory formation even in the absence of viral infection. Finally, I find that memory CD4 T cell formation following cold-adapted influenza vaccination is boosted when Ag is administered at this stage. These findings imply that persistence of viral Ag presentation into the effector phase is the key factor that determines the efficiency of memory generation. They also suggest that administering Ag during the effector stage may improve vaccine efficacy.
Influenza A virus matrix protein 1-specific human CD8+ T-cell response induced in trivalent inactivated vaccine recipientsTerajima, Masanori; Cruz, John; Leporati, Anita M.; Orphin, Laura; Babon, Jenny Aurielle B.; Co, Mary Dawn T.; Pazoles, Pamela P.; Jameson, Julie Marie; Ennis, Francis A. (2008-07-11)Among 17 HLA-A2-positive healthy adults, CD8+ T-cell responses against an HLA-A2-restricted matrix protein 1 (M1) epitope increased after immunization with trivalent inactivated influenza vaccine (TIV) in two individuals. The presence of M1 in TIV was confirmed by Western blotting. T-cell cytotoxicity assays showed that TIV is processed and the epitope is presented by antigen-presenting cells to an M1 epitope-specific CD8+ T-cell line for specific lysis. These data show that TIV, which is formulated to contain surface glycoproteins to induce serotype-specific antibody responses, also contains M1, capable of inducing subtype cross-reactive CD8+ T-cell responses in some vaccinees.