scholarly journals Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population

2018 ◽  
Author(s):  
Joshua G. Petrie ◽  
Emily T. Martin ◽  
Rachel Truscon ◽  
Emileigh Johnson ◽  
Caroline K. Cheng ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Influenza A ◽  
Influenza Infection ◽  
Geometric Mean ◽  
Influenza Vaccines ◽  
Respiratory Illnesses ◽  
Illness Onset ◽  
Correlates Of Protection ◽  
Antibody Titers ◽  
H3n2 Vaccine

ABSTRACTBackgroundInfluenza vaccines are important for prevention of influenza-associated hospitalization. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness evaluations in hospitalized populations.MethodsSerum specimens collected at admission from adults hospitalized for treatment of acute respiratory illnesses during two influenza seasons were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated the suitability of these specimens as proxies for pre-infection immune status, and measured associations between antibody titers and influenza vaccination and infectionResultsSpecimens were collected within 3 days of illness onset from 65% of participants; geometric mean titers (GMTs) did not vary by day of collection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated participants. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016.ConclusionsSerum collected after hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.

scholarly journals Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season

2018 ◽  
Author(s):  
Min Z. Levine ◽  
Emily T. Martin ◽  
Joshua G. Petrie ◽  
Adam S. Lauring ◽  
Crystal Holiday ◽  
...  
Keyword(s):  
Hong Kong ◽  
Influenza A ◽  
Geometric Mean ◽  
Fold Increase ◽  
Vaccine Effectiveness ◽  
Similar Increase ◽  
Illness Onset ◽  
Antibody Titers ◽  
H3n2 Vaccine ◽  
Independent Effects

ABSTRACTBackgroundThe 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.MethodsSerum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.ResultsMN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.ConclusionAlthough individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.

scholarly journals Frailty Is Associated With Increased Hemagglutination-Inhibition Titers in a 4-Year Randomized Trial Comparing Standard- and High-Dose Influenza Vaccination

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Nathalie Loeb ◽  
Melissa K Andrew ◽  
Mark Loeb ◽  
George A Kuchel ◽  
Laura Haynes ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Hemagglutination Inhibition ◽  
Influenza A ◽  
Standard Dose ◽  
Geometric Mean ◽  
Frailty Index ◽  
Antibody Responses ◽  
High Dose ◽  
Antibody Titers ◽  
The Impact

Abstract Background Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses. Methods We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index. Results Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients. Conclusions Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation.

scholarly journals Immunogenicity and safety of a trivalent inactivated influenza vaccine

2011 ◽  
Vol 51 (1) ◽  
pp. 22 ◽  
Author(s):  
Eddy Fadlyana ◽  
Kusnandi Rusmil ◽  
Novilia Sjafri Bachtiar ◽  
Rachmat Gunadi ◽  
Hadyana Sukandar
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Geometric Mean ◽  
Deltoid Muscle ◽  
Influenza B ◽  
Serious Adverse Events ◽  
Blood Samples ◽  
Adolescents And Adults ◽  
Antibody Titers ◽  
Influenza Prevention

Background Trivalent inactivated influenza vaccines (TIV) containing antigens of two influenza A strains, A(H1N1) and A(H3N2), and one influenza B strain, are the standard {onnulation for influenza prevention. The vaccines must be updated annually to provide optimal protection against the predicted prevalent strains for the next influenza season.Objective To assess the immunogenidty and safety of the inactivated influenza vaccine (Flubio®) in adolescents and adults, 28 days after a single dose.Methods In this experimental, randomized, single-blind, bridging study, we included 60 healthy adolescents and adults. A single, 0.5 mL dose was administered intramuscularly in the deltoid muscle of the left ann. Blood samples were obtained before and 28 days after immunization. Standardized hemagglutination inhibition (HI) test was used to assess antibody response to influenza antigens.Results From January to February 2010, a total of 60 adolescents and adults enrolled in the study, but two participants did not provide the required blood samples. One hundred percent of the subjects had an anti-influenza titer ≥ 1:40 HI units to all three strains, A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Brisbane/60/2008 (P=1.000) after immunization. The Geometric Mean Titers (GMT) after immunization increasedfor all strains: A/Brisbane, 76.4 to 992.7, A/Uruguay, 27.6 to 432.1, and B/Brisbane, 19.9 to 312.7. Twenty eight days after immunization, we found a 4 times increase in antibody titers in 75.8% of the subjects for A/Brisbane, 84.5% for A/Uruguay, and 77.6% for B/Brisbane. We also observed that 100% of seronegative subjects converted to seropositive for all 3 strains. All vaccines were well-tolerated. There were no serious adverse events reported during the study.Conclusion In adolescents and adults, the Flubio® vaccine was immunogenic and safe.

scholarly journals Immunogenicity of a Monovalent Pandemic Influenza A H1N1 Virus Vaccine with or without Prior Seasonal Influenza Vaccine Administration

2012 ◽  
Vol 19 (10) ◽  
pp. 1690-1692 ◽  
Author(s):  
Hidetoshi Igari ◽  
Akira Watanabe ◽  
Shunsuke Segawa ◽  
Akiko Suzuki ◽  
Mariko Watanabe ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Pandemic Influenza ◽  
Influenza A ◽  
H1n1 Virus ◽  
Geometric Mean ◽  
Vaccine Administration ◽  
Trivalent Influenza Vaccine ◽  
Influenza A H1n1 ◽  
Significant Difference ◽  
Antibody Titers

ABSTRACTThe immunogenicity of pandemic influenza A H1N1 virus (A/H1pdm) vaccine might be modified by prior seasonal trivalent influenza vaccine (sTIV) administration. We conducted a retrospective analysis of immunogenicity of 243 health care workers (number of sTIV-positive [sTIV+] subjects, 216; number of sTIV−subjects, 27) by hemagglutination inhibition. There was no significant difference in the ratios of antibody titers of ≥40 (41.2% versus 48.1%;P= 0.49) and fold increases in geometric mean titer (3.8 versus 4.5;P= 0.37). sTIV injected 7 to 10 days prior to A/H1pdm vaccine administration did not interfere with the immunogenicity of the latter.

scholarly journals Comparison of Serum Hemagglutinin and Neuraminidase Inhibition Antibodies After 2010–2011 Trivalent Inactivated Influenza Vaccination in Healthcare Personnel

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Maryrose R. Laguio-Vila ◽  
Mark G. Thompson ◽  
Sue Reynolds ◽  
Sarah M. Spencer ◽  
Manjusha Gaglani ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Infection ◽  
Fold Increase ◽  
Healthcare Personnel ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Duration Of Illness ◽  
Antibody Titers ◽  
Influenza Vaccinations

Abstract Background.  Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA. Methods.  Serum of 1349 healthcare personnel (HCP) electing or declining the 2010–2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection. Results.  In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009–2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections. Conclusions.  Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity.

scholarly journals Impact of Immune Priming, Vaccination, and Infection on Influenza A(H3N2) Antibody Landscapes in Children

2020 ◽  
Author(s):  
Michael Hinojosa ◽  
Samuel S Shepard ◽  
Jessie R Chung ◽  
Jennifer P King ◽  
Huong Q McLean ◽  
...  
Keyword(s):  
Influenza A ◽  
Antibody Responses ◽  
Influenza Vaccines ◽  
Infection Status ◽  
Immune Priming ◽  
Age Related ◽  
Vaccine Antigens ◽  
Inhibition Antibody ◽  
Antibody Titers ◽  
Virus Influenza

Abstract Background Preexisting antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination. Methods We enrolled 72 children (aged 7–17 years) in 2015–2016; all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014–2015, with 12 becoming infected with A(H3N2) in 2014–2015. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and postvaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015. Results The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Postvaccination titers were the highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Prevaccination titers to the vaccine were the strongest predictors of postvaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2)-infected children in 2014–2015 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015–2016 vaccination. Conclusions A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection.

scholarly journals A Live Attenuated Influenza Vaccine Elicits Enhanced Heterologous Protection When the Internal Genes of the Vaccine Are Matched to Those of the Challenge Virus

2019 ◽  
Vol 94 (4) ◽  
Author(s):  
Andrew Smith ◽  
Laura Rodriguez ◽  
Maya El Ghouayel ◽  
Aitor Nogales ◽  
Jeffrey M. Chamberlain ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Temperature Sensitive ◽  
Live Attenuated Influenza Vaccine ◽  
Cell Immunity

ABSTRACT Influenza A virus (IAV) causes significant morbidity and mortality, despite the availability of viral vaccines. The efficacy of live attenuated influenza vaccines (LAIVs) has been especially poor in recent years. One potential reason is that the master donor virus (MDV), on which all LAIVs are based, contains either the internal genes of the 1960 A/Ann Arbor/6/60 or the 1957 A/Leningrad/17/57 H2N2 viruses (i.e., they diverge considerably from currently circulating strains). We previously showed that introduction of the temperature-sensitive (ts) residue signature of the AA/60 MDV into a 2009 pandemic A/California/04/09 H1N1 virus (Cal/09) results in only 10-fold in vivo attenuation in mice. We have previously shown that the ts residue signature of the Russian A/Leningrad/17/57 H2N2 LAIV (Len LAIV) more robustly attenuates the prototypical A/Puerto Rico/8/1934 (PR8) H1N1 virus. In this work, we therefore introduced the ts signature from Len LAIV into Cal/09. This new Cal/09 LAIV is ts in vitro, highly attenuated (att) in mice, and protects from a lethal homologous challenge. In addition, when our Cal/09 LAIV with PR8 hemagglutinin and neuraminidase was used to vaccinate mice, it provided enhanced protection against a wild-type Cal/09 challenge relative to a PR8 LAIV with the same attenuating mutations. These findings suggest it may be possible to improve the efficacy of LAIVs by better matching the sequence of the MDV to currently circulating strains. IMPORTANCE Seasonal influenza infection remains a major cause of disease and death, underscoring the need for improved vaccines. Among current influenza vaccines, the live attenuated influenza vaccine (LAIV) is unique in its ability to elicit T-cell immunity to the conserved internal proteins of the virus. Despite this, LAIV has shown limited efficacy in recent years. One possible reason is that the conserved, internal genes of all current LAIVs derive from virus strains that were isolated between 1957 and 1960 and that, as a result, do not resemble currently circulating influenza viruses. We have therefore developed and tested a new LAIV, based on a currently circulating pandemic strain of influenza. Our results show that this new LAIV elicits improved protective immunity compared to a more conventional LAIV.

Effectiveness of trivalent and monovalent influenza vaccines against laboratory-confirmed influenza infection in persons with medically attended influenza-like illness in Bavaria, Germany, 2010/2011 season

2012 ◽  
Vol 141 (9) ◽  
pp. 1807-1815 ◽  
Author(s):  
H. ENGLUND ◽  
H. CAMPE ◽  
W. HAUTMANN
Keyword(s):  
Influenza A ◽  
Case Control Study ◽  
Influenza Infection ◽  
Influenza Vaccines ◽  
Influenza Like Illness ◽  
Negative Case ◽  
Influenza A H1n1 ◽  
Study Population ◽  
Group Sex ◽  
Control Study

SUMMARYWe estimated the vaccine effectiveness (VE) of trivalent and monovalent influenza vaccines, respectively, against laboratory-confirmed influenza infections in patients with influenza-like illness who visited physicians participating in the Bayern Influenza Sentinel in Bavaria, Germany during 2010/2011. Swab specimens were analysed for influenza A(H1N1)pdm09, A(H3) and B by PCR. VE was estimated using the test-negative case-control study design and logistic regression. In total, 1866 patients (790 cases, 1076 controls) were included. The VE of trivalent vaccines administered in season 2010/2011 against laboratory-confirmed infection with any influenza virus, adjusted for age group, sex, chronic illness and week of arrival of the specimen, was 67·8% [95% confidence interval (CI) 39·2–82·9)]. The adjusted VE of monovalent influenza vaccines administered in season 2009/2010 against laboratory-confirmed influenza A(H1N1)pdm09 infection in 2010/2011 was 38·6% (95% CI −70·0 to 77·8). This is the first VE study conducted in Bavaria. We concluded that the trivalent influenza vaccines were effective in our study population.

scholarly journals Comparison of the neuraminidase antigenicity in recently circulating influenza A and vaccine viruses

2021 ◽  
Author(s):  
Jin Gao ◽  
Xing Li ◽  
Hongquan Wan ◽  
Zhiping Ye ◽  
Robert Daniels
Keyword(s):  
Northern Hemisphere ◽  
Influenza A ◽  
Influenza Season ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Strain Selection ◽  
Reverse Genetic ◽  
Protective Response ◽  
C Terminus ◽  
H3n2 Vaccine

Neuraminidase (NA or N) antigens in circulating influenza viruses are not extensively evaluated for vaccine strain selection like hemagglutinin (HA or H) even though viral-based influenza vaccines include the recommended strain NA in varying amounts. As NA can also elicit a protective response, we assessed the antigenic similarity of the NAs from human H1N1 and H3N2 viruses that were prevalent between September 2019 to December 2020 to NAs from several recently recommended vaccine strains. To eliminate the dependence on isolates, the enzyme-linked lectin assay for analyzing NA antigenicity was performed with reverse genetic viruses carrying the same HA. Our results show that ferret antisera against NAs from the recommended H1N1 and H3N2 vaccine strains for the 2020-21 northern hemisphere influenza season recognize and inhibit the most prevalent circulating N1s and N2s, suggesting the NAs from the influenza A vaccine and circulating strains are antigenically similar. Comparisons of the recent N2s also revealed a bias in the reactivity of NA antisera from the egg and cell-based H3N2 vaccine strains due to a C-terminal substitution, indicating the C-terminus can influence N2 antigenicity and should receive consideration during the H3N2 strain selection.

scholarly journals Attenuated influenza A vaccine (Alice) in an adult population: vaccine-related illness, serum and nasal antibody production, and intrafamily transmission

1975 ◽  
Vol 2 (5) ◽  
pp. 403-409
Author(s):  
T E Minor ◽  
E C Dick ◽  
C R Dick ◽  
S L Inhorn
Keyword(s):  
Influenza A ◽  
Recombinant Strain ◽  
Nasal Congestion ◽  
Adult Population ◽  
Geometric Mean ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Primary Vaccination ◽  
Clinical Signs And Symptoms ◽  
H3n2 Vaccine

Ninety-five healthy adults, ages 18 to 56 years, received two intranasal doses, 2 weeks apart, of a live, attenuated, influenza type A (H3N2) vaccine (an inhibitor-resistant recombinant strain of A/England/42/72 named "Alice"). Ninety-two persons were given placebos similarly. Ninety-three percent of 68 subjects with initial serum hemagglutination-inhibition (HI) titers of greater than or equal to 1:40 to influenza A (H3N2) had a fourfold or greater antibody increase in postvaccination sera. Forty-four percent of 27 subjects with an initial HI titer of greater than or equal to 1:80 had similar increases. Overall, 77% of vaccinees had fourfold or greater antibody titer increases. Vaccinees had geometric mean serum HI titers (GMT) of 1:26, 1:123, and 1:166 at 0, 14, and 30 days, respectively. The GMTs for placebos were 1:21, 1:22, and 1:21. Thirty-five vaccinees were examined for both serum and nasal antibody; 89% had significant increases in one or both. Nasal antibody response was directly related to the level of initial serum HI titer in that 83% of 12 persons with prevaccination HI titers of 1:80 greater than or equal to 1:80 showed significant nasal antibody rises, whereas only 61% of the remaining 23 subjects with prevaccination HI titers of less than or equal to 1:40 did so. The number and severity of clinical signs and symptoms reported by vaccinees and placebos did not differ significantly. The greatest differences noted between groups were for nasal congestion on days 0 to 6 (8.3%) and rhinitis on days 14 to 20 (5.9%). Four vaccinees shed Alice after primary vaccination, but viral titers were low (10 to 100 tissue culture-infective doses/ml). One member in each of 15 cohabiting male-female couples received Alice while the other received a placebo; one of the placebo members had significant increases in serum and nasal antibody, indicating a possible transmission.

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