Preexisting Subtype Immunodominance Shapes Memory B Cell Recall Response to Influenza Vaccination

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2019 Dec 4

PMID 31794433

Citations 35

Authors

Rodrigo B Abreu

Greg A Kirchenbaum

Emily F Clutter

Giuseppe A Sautto

Ted M Ross

Affiliations

Soon will be listed here.

Abstract

Influenza is a highly contagious viral pathogen with more than 200,000 cases reported in the United States during the 2017-2018 season. Annual vaccination is recommended by the World Health Organization, with the goal to reduce influenza severity and transmission. Currently available vaccines are about 60% effective, and vaccine effectiveness varies from season to season, as well as between different influenza subtypes within a single season. Immunological imprinting from early-life influenza infection can prominently shape the immune response to subsequent infections. Here, the impact of preexisting B cell memory in the response to quadrivalent influenza vaccine was assessed using blood samples collected from healthy subjects (18-85 years old) prior to and 21-28 days following influenza vaccination. Influenza vaccination increased both HA-specific antibodies and memory B cell frequency. Despite no apparent differences in antigenicity between vaccine components, most individuals were biased toward one of the vaccine strains. Specifically, responses to H3N2 were reduced in magnitude relative to the other vaccine components. Overall, this study unveils a potentially new mechanism underlying differential vaccine effectiveness against distinct influenza subtypes.

Citing Articles

Exploring bias due to below-limit-of-detection values in influenza vaccine antibody modeling: A case study and instructional guide for the CIVIC study.

Ge Y, Handel A, Giabbanelli P, Lemacks J, Greer T, Raynee P Vaccine. 2025; 49:126802.

PMID: 39908720 PMC: 11875013. DOI: 10.1016/j.vaccine.2025.126802.

Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection.

Chen Z, Huang H, Wang X, Schon K, Jia Y, Lebens M Nat Commun. 2025; 16(1):432.

PMID: 39788944 PMC: 11718266. DOI: 10.1038/s41467-024-55193-y.

Computationally Optimized Hemagglutinin Proteins Adjuvanted with Infectimune Generate Broadly Protective Antibody Responses in Mice and Ferrets.

Allen J, Zhang X, Medina J, Thomas M, Lynch A, Nelson R Vaccines (Basel). 2025; 12(12.

PMID: 39772026 PMC: 11679666. DOI: 10.3390/vaccines12121364.

Impact of Viral Lower Respiratory Tract Infection (LRTI) in Early Childhood (0-2 Years) on Lung Growth and Development and Lifelong Trajectories of Pulmonary Health: A National Institutes of Health (NIH) Workshop Summary.

Deshmukh H, Whitsett J, Zacharias W, Way S, Martinez F, Mizgerd J Pediatr Pulmonol. 2024; 60(1):e27357.

PMID: 39565217 PMC: 11740654. DOI: 10.1002/ppul.27357.

Multiplexed Antibody Sequencing and Profiling of the Human Hemagglutinin-specific Memory B Cell Response following Influenza Vaccination.

Raju N, Kramer K, Cavallaro M, Diotti R, Shiakolas A, Campos Mota Y J Immunol. 2024; 213(11):1605-1619.

PMID: 39441352 PMC: 11573632. DOI: 10.4049/jimmunol.2400326.

References

Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W . Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013; 19(10):1305-12. DOI: 10.1038/nm.3350. View

Zost S, Parkhouse K, Gumina M, Kim K, Diaz Perez S, Wilson P . Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A. 2017; 114(47):12578-12583. PMC: 5703309. DOI: 10.1073/pnas.1712377114. View

MAYNARD J, Dull H, Hanson M, FELTZ E, Berger R, Hammes L . Evaluation of monovalent and polyvalent influenza vaccines during an epidemic of type A2 and B influenza. Am J Epidemiol. 1968; 87(1):148-57. DOI: 10.1093/oxfordjournals.aje.a120795. View

Cai S, Temkin-Greener H . Influenza vaccination and its impact on hospitalization events in nursing homes. J Am Med Dir Assoc. 2011; 12(7):493-8. PMC: 3661218. DOI: 10.1016/j.jamda.2010.03.005. View

Simonsen L, Reichert T, Viboud C, Blackwelder W, Taylor R, Miller M . Impact of influenza vaccination on seasonal mortality in the US elderly population. Arch Intern Med. 2005; 165(3):265-72. DOI: 10.1001/archinte.165.3.265. View

DiazGranados C, Dunning A, Kimmel M, Kirby D, Treanor J, Collins A . Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014; 371(7):635-45. DOI: 10.1056/NEJMoa1315727. View

Jegaskanda S, Luke C, Hickman H, Sangster M, Wieland-Alter W, McBride J . Generation and Protective Ability of Influenza Virus-Specific Antibody-Dependent Cellular Cytotoxicity in Humans Elicited by Vaccination, Natural Infection, and Experimental Challenge. J Infect Dis. 2016; 214(6):945-52. PMC: 4996149. DOI: 10.1093/infdis/jiw262. View

BASHE Jr W, STEGMILLER H, LEONIDA D, Greenwald P . FAILURE OF POLYVALENT VACCINE TO PROVIDE CLINICAL PROTECTION AGAINST ASIAN INFLUENZA. N Engl J Med. 1964; 270:870-4. DOI: 10.1056/NEJM196404232701703. View

Berton M, Webster R . The antigenic structure of the influenza B virus hemagglutinin: operational and topological mapping with monoclonal antibodies. Virology. 1985; 143(2):583-94. DOI: 10.1016/0042-6822(85)90396-4. View

10.

Cheng X, Zengel J, Suguitan Jr A, Xu Q, Wang W, Lin J . Evaluation of the humoral and cellular immune responses elicited by the live attenuated and inactivated influenza vaccines and their roles in heterologous protection in ferrets. J Infect Dis. 2013; 208(4):594-602. DOI: 10.1093/infdis/jit207. View

11.

Faenzi E, Zedda L, Bardelli M, Spensieri F, Borgogni E, Volpini G . One dose of an MF59-adjuvanted pandemic A/H1N1 vaccine recruits pre-existing immune memory and induces the rapid rise of neutralizing antibodies. Vaccine. 2012; 30(27):4086-94. DOI: 10.1016/j.vaccine.2012.04.020. View

12.

Blomberg B, Frasca D . Quantity, not quality, of antibody response decreased in the elderly. J Clin Invest. 2011; 121(8):2981-3. PMC: 3148749. DOI: 10.1172/JCI58406. View

13.

Blanton L, Mustaquim D, Alabi N, Kniss K, Kramer N, Budd A . Update: Influenza Activity - United States, October 2, 2016-February 4, 2017. MMWR Morb Mortal Wkly Rep. 2017; 66(6):159-166. PMC: 5657859. DOI: 10.15585/mmwr.mm6606a2. View

14.

Pillet S, Kobasa D, Meunier I, Gray M, Laddy D, Weiner D . Cellular immune response in the presence of protective antibody levels correlates with protection against 1918 influenza in ferrets. Vaccine. 2011; 29(39):6793-801. DOI: 10.1016/j.vaccine.2010.12.059. View

15.

Goodwin K, Viboud C, Simonsen L . Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. 2005; 24(8):1159-69. DOI: 10.1016/j.vaccine.2005.08.105. View

16.

Monto A, Malosh R, Petrie J, Martin E . The Doctrine of Original Antigenic Sin: Separating Good From Evil. J Infect Dis. 2017; 215(12):1782-1788. PMC: 5853211. DOI: 10.1093/infdis/jix173. View

17.

Smith J, Lipsitch M, Almond J . Vaccine production, distribution, access, and uptake. Lancet. 2011; 378(9789):428-38. PMC: 3164579. DOI: 10.1016/S0140-6736(11)60478-9. View

18.

Suptawiwat O, Ninpan K, Boonarkart C, Ruangrung K, Auewarakul P . Evolutionary dynamic of antigenic residues on influenza B hemagglutinin. Virology. 2016; 502:84-96. DOI: 10.1016/j.virol.2016.12.015. View

19.

Sanz I, Wei C, Lee F, Anolik J . Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol. 2008; 20(1):67-82. PMC: 2440717. DOI: 10.1016/j.smim.2007.12.006. View

20.

Huang K, Rijal P, Schimanski L, Powell T, Lin T, McCauley J . Focused antibody response to influenza linked to antigenic drift. J Clin Invest. 2015; 125(7):2631-45. PMC: 4613558. DOI: 10.1172/JCI81104. View