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

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.

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

10.1101/416628 ◽

2018 ◽

Cited By ~ 3

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.

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Comparison of Immune Response to the Influenza Vaccine in Obese and Nonobese Healthcare Workers

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2014.59 ◽

2015 ◽

Vol 36 (3) ◽

pp. 249-253 ◽

Cited By ~ 4

Author(s):

Michael A. Sweet ◽

Jonathan A. McCullers ◽

Paul R. Lasala ◽

Frank E. Briggs ◽

Anne Smithmyer ◽

...

Keyword(s):

Influenza Vaccine ◽

Healthcare Workers ◽

Influenza A ◽

Medical Center ◽

Geometric Mean ◽

Fold Increase ◽

Influenza B ◽

Influenza A H1n1 ◽

Significant Difference ◽

Antibody Titers

OBJECTIVETo determine whether there is a difference in antibody titers and functionality after receipt of the influenza vaccine for obese versus nonobese healthcare workers (HCW).DESIGNProspective observational study.SETTINGTertiary medical center.PARTICIPANTSHealthcare workers.METHODSBaseline influenza antibody titers for obese and nonobese HCW were recorded during the hospital’s 2011 annual influenza vaccination day and follow-up antibody titers were measured 4 weeks later. Antibodies were measured using the hemagglutination inhibition assay and functionality was measured using the micro-neutralization method.RESULTSOf 200 initial HCWs, 190 completed the study (97 obese and 93 nonobese). Seroprotection after immunization was not significantly different for nonobese compared with obese HCW for each strain (influenza A [H1N1], 99% and 99%; influenza A [H3N2], 100% and 99%; and influenza B, 67% and 71%, respectively)All geometric mean titers measured by micro-neutralization showed statistically significant increases in activity. In comparison, there was no difference in the 4-fold increase in H1N1 or B titers. There was a significant difference in the 4-fold increase of H3N2 titers between the nonobese and obese HCWs (82/93 [88%] vs 64/97 [66%], P=.003)In an ad hoc analysis we found that obese HCWs had a statistically greater number of 4-fold decreases in titers with H1N1 and H3N2.CONCLUSIONSThere was no significant difference in protection from influenza between obese and nonobese HCWs after immunization.Infect Control Hosp Epidemiol 2014;00(0): 1–5

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa148 ◽

2020 ◽

Vol 7 (5) ◽

Cited By ~ 3

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.

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Immunogenicity and safety of a trivalent inactivated influenza vaccine

Paediatrica Indonesiana ◽

10.14238/pi51.1.2011.22-8 ◽

2011 ◽

Vol 51 (1) ◽

pp. 22 ◽

Cited By ~ 1

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.

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Haemagglutination-inhibiting (HI) antibodies against four prototype strains of influenza A virus in different age groups

Journal of Hygiene ◽

10.1017/s0022172400025638 ◽

1979 ◽

Vol 82 (2) ◽

pp. 225-230 ◽

Cited By ~ 1

Author(s):

A. L. Terzin ◽

S. Djurišić ◽

B. Vuković ◽

V. Vujkov

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

New Jersey ◽

Antibody Response ◽

Influenza A ◽

Geometric Mean ◽

Age Groups ◽

The Other ◽

Younger Age ◽

Lower Antibody Response

SUMMARYSera of 197 apparently well persons were tested for residual haemagglutination-inhibiting antibodies against live Hong Kong/68, A/FM/47 and A/PR/34 strains. Sera of 62 well persons, regularly exposed to contacts with swine, were tested against an inactivated A/New Jersey/76 antigen.Those born some time before and during a certain influenza era showed a significantly greater proportion of homologous residual titres against the subtype prevailing in that influenza era, than those born after the termination of the same era.In each of the seven age groups tested both the percentage of positives and the geometric mean titres were usually highest against the Hong Kong strain (representing the most recent era); the next highest were those against the FM1 strain and the lowest were those against the PR8 strain (representing the most distant of these three influenza eras).The serological involvement of donors exposed to regular contacts with swine was relatively stronger against the New Jersey antigen than the response of other serum donors shown against the other three, more recent, prototypes of influenza virus A. The oldest age groups showed significantly lower antibody response against the PR8, FM1 and Hong Kong strains (but not against the New Jersey antigen) than the next one or two of the younger age groups.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00077-12 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1690-1692 ◽

Cited By ~ 1

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.

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Influenza Vaccine Effectiveness by A(H3N2) Phylogenetic Subcluster and Prior Vaccination History: 2016–2017 and 2017–2018 Epidemics in Canada

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa138 ◽

2020 ◽

Author(s):

Danuta M Skowronski ◽

Siobhan Leir ◽

Suzana Sabaiduc ◽

Catharine Chambers ◽

Macy Zou ◽

...

Keyword(s):

Confidence Interval ◽

Influenza Vaccine ◽

Influenza A ◽

Vaccine Effectiveness ◽

Glycosylation Sites ◽

Vaccination History ◽

H3n2 Vaccine

Abstract Background The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015–2016 to 3C.2a for 2016–2017 and 2017–2018. Circulating 3C.2a viruses showed considerable hemagglutinin glycoprotein diversification and the egg-adapted vaccine also bore mutations. Methods Vaccine effectiveness (VE) in 2016–2017 and 2017–2018 was assessed by test-negative design, explored by A(H3N2) phylogenetic subcluster and prior season’s vaccination history. Results In 2016–2017, A(H3N2) VE was 36% (95% confidence interval [CI], 18%–50%), comparable with (43%; 95% CI, 24%–58%) or without (33%; 95% CI, −21% to 62%) prior season’s vaccination. In 2017–2018, VE was 14% (95% CI, −8% to 31%), lower with (9%; 95% CI, −18% to 30%) versus without (45%; 95% CI, −7% to 71%) prior season’s vaccination. In 2016–2017, VE against predominant clade 3C.2a1 viruses was 33% (95% CI, 11%–50%): 18% (95% CI, −40% to 52%) for 3C.2a1a defined by a pivotal T135K loss of glycosylation; 60% (95% CI, 19%–81%) for 3C.2a1b (without T135K); and 31% (95% CI, 2%–51%) for other 3C.2a1 variants (with/without T135K). VE against 3C.2a2 viruses was 45% (95% CI, 2%–70%) in 2016–2017 but 15% (95% CI, −7% to 33%) in 2017–2018 when 3C.2a2 predominated. VE against 3C.2a1b in 2017–2018 was 37% (95% CI, −57% to 75%), lower at 12% (95% CI, −129% to 67%) for a new 3C.2a1b subcluster (n = 28) also bearing T135K. Conclusions Exploring VE by phylogenetic subcluster and prior vaccination history reveals informative heterogeneity. Pivotal mutations affecting glycosylation sites, and repeat vaccination using unchanged antigen, may reduce VE.

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Good but Variable Humoral Response to Trivalent Influenza Vaccination in Patients with Non-Hodgkin’s Lymphoma - Two Seasons Experience.

Blood ◽

10.1182/blood.v106.11.4685.4685 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4685-4685

Author(s):

Piotr Centkowski ◽

Lidia Brydak ◽

Magdalena Machala ◽

Ewa Kalinka ◽

Maria Blasinska-Morawiec ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza Vaccination ◽

Geometric Mean ◽

Humoral Response ◽

Fold Increase ◽

Treated Group ◽

Influenza Hemagglutinin ◽

Protection Rate ◽

Antibody Titers ◽

Previously Treated

Abstract We assessed humoral response to influenza vaccination (vacc) in two consecutive seasons 2003/2004 and 2004/2005 in 123 NHL patients. In season 03/04 50 patients (29 previously treated with chemotherapy - group A03/04 and 21 not treated - group B03/04) and 73 patients in season 04/05: 34 treated - A04/05, 39 not treated - B04/05 were vaccinated with trivalent subunit influenza vaccine. Antibody responses to influenza hemagglutinin (HI) and neuraminidase (NI) were determined in sera collected before vacc, after 1 month and after 6 months. One month after vacc geometric mean antibody titers (GMTs) of antiHI antibodies significantly increased (p<0.05) and mean fold increases (MFIs) ranged from 10.4 to 24.3 in A03/04, 10.9–11.7 in A04/05, 6.5–31.6 in B03/04 and 14.8–21 in B04/05, than fell after 6 months to 3.6–7.8 in A03/04, 3.7–4.4 in A04/05, 1.7–11.2 in B03/04 and 7.8–8.5 in B04/05. Prevacc protection rate, i.e. the number of subjects with the protective HI antibody titers >1:40, ranged from 3.4 to 10.3% in A03/04, 2.9-8.8% in A04/05, 0–4.6% in B03/04 and 0–5.1% in B04/05. After 1 month protection rates ranged from 78.1 to 87.5% in A03/04, 61.8–70.6% in A04/05, 73.3–93.3% in B03/04 and 66.7–74.4% in B04/05 and decreased after 6 months to 24.1–37.9% in A03/04, 32.4–35.3% in A04/05, 19–47.6% in B03/04 and 17.9–35.9% in B04/05. Response rates, i.e. the number of subjects with at least a 4-fold increase of antiHI antibody titers after vacc, ranged from 58.6–75.9% in A03/04, 50–67.6% in A04/05, 57.1–81% in B03/04 and 61.5–71.8% in B04/05. Six months after vacc it decreased to 17.2–34.5% in A03/04, 20.6–29.4% in A04/05, 19–38.1% in B03/04 and 15.4–33.3% in B04/05. In all patients’ groups, post-vacc antiNI GMTs were significantly higher (p<0.05) than pre-vacc. MFIs of antiNI antibodies 1 month after vacc ranged from 11 to 17.5 in A03/04, 4.1–9.4 in A04/05, 5.1–9.9 in B03/04 and 6.3–9.9 in B04/05, then fell to 2.9–6.9 in A03/04, 1.3–5.1 in A04/05, 3.4–4.9 in B03/04 and 2.8–3.6 in B04/05. In season 03/04 only hemagglutinin H1 antibody titers were significantly higher in CTR than in patients in contrast of season 04/05 when in patients the titers of H1, H3 and N1, N2, NB were significantly lower. We conclude that the response to influenza vaccine is similar in patients previously treated and not-treated with chemoterapy. It is highly immunogenic in NHL patients, but the level of specific antibodies is variable and may depend on immunogenecity of vaccine for actual season. After 6 months the antibody titers rapidly decline, thus the NHL patients may need the second dose of vaccine to maintain good protective level.

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988. Effectiveness of Seasonal Influenza Vaccines Against Influenza A(H3N2) Illness Among Children Aged <18 Years, US Flu VE Network, 2010–2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.825 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S292-S292

Author(s):

Brendan L Flannery ◽

Jessie Chung ◽

Michael L Jackson ◽

Lisa A Jackson ◽

Arnold S Monto ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Older Children ◽

Research Support ◽

Illness Onset ◽

Negative Controls ◽

Research Grant

Abstract Background Interim estimates of 2017–2018 influenza vaccine effectiveness (VE) against influenza A(H3N2)-related illness in the United States indicated better protection among young children than among older children and adolescents. We examined VE against influenza A(H3N2) illness during five A(H3N2)-predominant seasons from 2010–2011 through 2016–2017 to investigate differences between VE among younger vs. older children. Methods We analyzed data from 11,736 outpatients aged <18 years with medically attended acute respiratory illnesses enrolled at US Flu VE Network study sites during five influenza A(H3N2)-predominant seasons. Respiratory specimens from all enrollees were tested for influenza viruses using reverse transcription PCR. Children with documented receipt of the recommended number of doses of current season inactivated influenza vaccine at least 14 days before illness onset were considered fully vaccinated; partially vaccinated children and those who received live attenuated influenza vaccine were excluded. Vaccine effectiveness was estimated as 100 × (1 – adjusted odds ratio) from multivariable logistic regression adjusting for study site, age, sex, presence of high-risk medical conditions, and days from illness onset to enrollment comparing odds of vaccination among A(H3N2)-positive cases vs. influenza-negative controls. Results A total of 1,854 influenza A(H3N2) cases and 9,882 influenza-negative controls were included; 494 (28%) influenza A(H3N2) cases and 3,637 (41%) controls were fully vaccinated before illness onset. VE ranged from 26% (95% confidence interval [CI], −17% to 53%) to 60% (38%–75%) among children aged 6 months–4 years and from 9% (−16% to 29%) to 66% (37%–82%) among 5–17 year olds (figure). During 2012–2013 and 2014–2015, A(H3N2) VE estimates were significantly higher among younger compared with older children (P < 0.05); in other seasons before 2017–2018, A(H3N2) VE estimates were similar among younger and older children. Conclusion Higher VE against A(H3N2) viruses in younger vs. older children in some seasons suggests immunologic differences in response to vaccine components. Overall, inactivated influenza vaccine provided moderate protection against A(H3N2)-related illness among children. Disclosures M. L. Jackson, sanofi pasteur: Grant Investigator, Research support. L. A. Jackson, Novartis: Grant Investigator, Research support. R. K. Zimmerman, sanofi pasteur: Grant Investigator, Research support. Pfizer: Grant Investigator, Research support. Merck: Grant Investigator, Research support. M. P. Nowalk, Merck: Grant Investigator, Research support. Pfizer: Grant Investigator, Research support. M. R. Griffin, MedImmune: Grant Investigator, Research support. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none. J. J. Treanor, Novartis: Board Member and Consultant, Consulting fee.

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Immunity to attenuated influenza virus WRL 105 infection induced by heterologous, inactivated influenza A virus vaccines

Journal of Hygiene ◽

10.1017/s0022172400053158 ◽

1977 ◽

Vol 79 (3) ◽

pp. 321-332 ◽

Cited By ~ 47

Author(s):

C. W. Potter ◽

R. Jennings ◽

K. Nicholson ◽

D. A. J. Tyrrell ◽

K. G. Dickinson

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Influenza A ◽

Serum Antibody ◽

Fold Increase ◽

Vaccine Virus ◽

Cross Reactivity ◽

Variable Response ◽

Challenge Virus ◽

Two Factors

SUMMARYGroups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16·6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4·2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.

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