Comparability of Titers of Antibodies against Seasonal Influenza Virus Strains as Determined by Hemagglutination Inhibition and Microneutralization Assays

ABSTRACT We compared titers of antibodies against A/H1N1, A/H3N2, and B influenza virus strains collected pre- and postvaccination using hemagglutination inhibition (HI) and microneutralization (MN) assays and data from two vaccine trials: study 1, performed with a cell-grown trivalent influenza vaccine (TIVc) using cell-grown target virus in both assays, and study 2, performed with an egg-grown adjuvanted quadrivalent influenza vaccine (aQIVe) using egg-grown target virus. The relationships between HI- and MN-derived log-transformed titers were examined using different statistical techniques. Deming regression analyses showed point estimates for slopes generally close to 1 across studies and strains. The slope of regression was closest to 1 for A/H3N2 strain when either cell- or egg-grown viral target virus was used. Bland-Altman plots indicated a very small percentage of results outside 2 and 3 standard deviations. The magnitudes and directions of differences between titers in the two assays varied by study and strain. Mean differences favored the MN assay for A/H1N1 and B strains in study 1, whereas the titers determined by HI were higher than those determined by MN against the A/H3N2 strain. In study 2, mean differences favored the MN assay for A/H3N2 and B strains. Overall, the directions and magnitudes of the mean differences were similar between the two vaccines. The concordance correlation coefficient values ranged from 0.74 (A/H1N1 strain, study 1) to 0.97 (A/H3N2 strain, study 1). The comparative analysis demonstrates an overall strong positive correlation between the HI and MN assays. These data support the use of the MN assay to quantify the immune response of influenza vaccines in clinical studies, particularly for the A/H3N2 strain.

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Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa181 ◽

2020 ◽

Author(s):

Jia-Qian Cao ◽

Peng-Fei Jin ◽

Zhao-Zhun Zeng ◽

Li Zhang ◽

Fan-Yue Meng ◽

...

Keyword(s):

Clinical Trials ◽

Influenza Virus ◽

Immune Responses ◽

Influenza Vaccine ◽

Hemagglutination Inhibition ◽

Cross Reactivity ◽

Vaccine Effectiveness ◽

Prior Exposure ◽

Post Vaccination ◽

Blood Samples

Abstract Background To investigate effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants. Method We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples before and 28 days after vaccination were collected and tested by hemagglutination-inhibition tests against both vaccine strains and circulating variants during the 2015–2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated. Results Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (Padjusted=0.038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.012). Antigenic distance was well-matched with serological results. Besides, age-specific differences in human post-vaccination responses against the identical circulating strain was noted. And children had most cross-reactive response to both H3N2 and B-yamagata subtypes. Conclusion Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific post-vaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human post-vaccination responses.

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High Preexisting Serological Antibody Levels Correlate with Diversification of the Influenza Vaccine Response

Journal of Virology ◽

10.1128/jvi.02871-14 ◽

2015 ◽

Vol 89 (6) ◽

pp. 3308-3317 ◽

Cited By ~ 74

Author(s):

Sarah F. Andrews ◽

Kaval Kaur ◽

Noel T. Pauli ◽

Min Huang ◽

Yunping Huang ◽

...

Keyword(s):

Influenza Virus ◽

B Cells ◽

Influenza Vaccine ◽

B Cell ◽

Cell Response ◽

Vaccine Response ◽

Trivalent Influenza Vaccine ◽

Antibody Levels ◽

Virus Strains ◽

B Cell Response

ABSTRACTReactivation of memory B cells allows for a rapid and robust immune response upon challenge with the same antigen. Variant influenza virus strains generated through antigenic shift or drift are encountered multiple times over the lifetime of an individual. One might predict, then, that upon vaccination with the trivalent influenza vaccine across multiple years, the antibody response would become more and more dominant toward strains consistently present in the vaccine at the expense of more divergent strains. However, when we analyzed the vaccine-induced plasmablast, memory, and serological responses to the trivalent influenza vaccine between 2006 and 2013, we found that the B cell response was most robust against more divergent strains. Overall, the antibody response was highest when one or more strains contained in the vaccine varied from year to year. This suggests that in the broader immunological context of viral antigen exposure, the B cell response to variant influenza virus strains is not dictated by the composition of the memory B cell precursor pool. The outcome is instead a diversified B cell response.IMPORTANCEVaccine strategies are being designed to boost broadly reactive B cells present in the memory repertoire to provide universal protection to the influenza virus. It is important to understand how past exposure to influenza virus strains affects the response to subsequent immunizations. The viral epitopes targeted by B cells responding to the vaccine may be a direct reflection of the B cell memory specificities abundant in the preexisting immune repertoire, or other factors may influence the vaccine response. Here, we demonstrate that high preexisting serological antibody levels to a given influenza virus strain correlate with low production of antibody-secreting cells and memory B cells recognizing that strain upon revaccination. In contrast, introduction of antigenically novel strains generates a robust B cell response. Thus, both the preexisting memory B cell repertoire and serological antibody levels must be taken into consideration in predicting the quality of the B cell response to new prime-boost vaccine strategies.

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Development of a Pan-H1 Influenza Vaccine

Journal of Virology ◽

10.1128/jvi.01349-18 ◽

2018 ◽

Vol 92 (22) ◽

Cited By ~ 15

Author(s):

Nicole Darricarrère ◽

Svetlana Pougatcheva ◽

Xiaochu Duan ◽

Rebecca S. Rudicell ◽

Te-Hui Chou ◽

...

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Influenza Vaccine ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Influenza Vaccines ◽

The Past ◽

Individual Strain ◽

Humoral Responses ◽

Virus Strains

ABSTRACT The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine. IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses.

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Targeting Antigens for Universal Influenza Vaccine Development

Viruses ◽

10.3390/v13060973 ◽

2021 ◽

Vol 13 (6) ◽

pp. 973

Author(s):

Quyen-Thi Nguyen ◽

Young-Ki Choi

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Influenza Viruses ◽

Target Antigen ◽

Cell Responses ◽

Universal Influenza Vaccine ◽

Virus Strains

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.

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Is It Possible? A Different Approach to Creating a Universal Influenza Vaccine

mBio ◽

10.1128/mbio.01580-15 ◽

2015 ◽

Vol 6 (5) ◽

Cited By ~ 1

Author(s):

Stacey Schultz-Cherry

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Seasonal Influenza ◽

Influenza Virus Infection ◽

Emerging Viruses ◽

The Public ◽

Influenza Virus Hemagglutinin ◽

Health Community ◽

Universal Influenza Vaccine ◽

Virus Strains

ABSTRACT The best way to combat influenza virus infection is to prevent it. However, the continual evolution of circulating influenza virus strains and the constant threat of newly emerging viruses forces the public health community to annually update seasonal influenza vaccines while stockpiling potential pandemic virus vaccines. Thus, there is an urgent need to develop a “universal” influenza vaccine that affords protection against all strains. In their recent article, L. M. Schwartzman et al. (mBio 6:e01044-15, 2015, doi:10.1128/mBio.01044-15) demonstrated that intranasal immunization of mice with a cocktail of viral-like particles (VLPs) expressing distinct influenza virus hemagglutinin (HA) proteins can broadly protect against infection not only with the same viral strains but also with unrelated strains. These findings suggest a promising strategy for developing a broadly protective “universal” influenza vaccine.

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Optimization of the Predicting of the Influenza Vaccine Strains

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2019-18-1-4-17 ◽

2019 ◽

Vol 18 (1) ◽

pp. 4-17 ◽

Cited By ~ 4

Author(s):

E. P. Kharchenko

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Influenza Season ◽

Hidden Markov ◽

Computational Method ◽

Human Influenza ◽

Data Bases ◽

Epidemic Season ◽

Incidence And Mortality ◽

Virus Strains

Relevance. Vaccination is still the most effective way to reduce the incidence and mortality from influenza and the complications it causes. WHO recommends the composition of the vaccine strain for each influenza season. Unfortunately, the relevance of vaccines and strains of influenza virus circulating during the epidemic season cannot always coincide. The cause is flu variability.Aim is to develop a new computational method for predicting an optimal hemagglutinin (HA) structure in H1N1 and H3N2 human influenza vaccine strains for coming epidemic seasons and to compare its results with WHO recommendations.Materials and method. For this study HA sequences were used from data bases available in INTERNET and the modified hidden Markov model was used to construct the HA primary structures.Results. It was indicated that the new bioinformatics approach allowed to construct an optimal structure of HA for vaccine strains. It was at most close to HA of circulating virus strains in coming epidemic seasons, spreaded over them and was superior to WHO recommendations. Conclusion: HA sequences should be considered as reliable background for predicting vaccine strains to decrease risks of not optimal and even mistakable choices. Bioinformatics approach allows to continually monitor HA changes after epidemics and to estimate adequacy of manufacturing vaccines to the future epidemic season.

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