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Immunogenicity, reactogenicity and safety of an inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine: a phase III, randomized trial in adults aged ≥18 years.

Kieninger D, Sheldon E, Lin WY, Yu CJ, Bayas JM, Gabor JJ, Esen M, Fernandez Roure JL, Narejos Perez S, Alvarez Sanchez C, Feng Y, Claeys C, Peeters M, Innis BL, Jain V - BMC Infect. Dis. (2013)

Bottom Line: This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection.For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%.QIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Two antigenically distinct influenza B lineages have co-circulated since the 1980s, yet inactivated trivalent influenza vaccines (TIVs) include strains of influenza A/H1N1, A/H3N2, and only one influenza B from either the Victoria or Yamagata lineage. This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection. Formulations including both influenza B lineages could improve protection against circulating influenza B viruses. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in adults in stable health.

Methods: A total of 4659 adults were randomized 5:5:5:5:3 to receive one dose of QIV (one of three lots) or a TIV containing either a B/Victoria or B/Yamagata strain. Hemagglutination-inhibition assays were performed pre-vaccination and 21-days after vaccination. Lot-to-lot consistency of QIV was assessed based on geometric mean titers (GMT). For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%. Reactogenicity and safety profile of each vaccine were assessed. Clinicaltrials.gov: NCT01204671.

Results: Consistent immunogenicity was demonstrated for the three QIV lots. QIV was non-inferior to TIV for the shared vaccine strains, and was superior for the added alternate-lineage B strains. QIV elicited robust immune responses against all four vaccine strains; the seroconversion rates were 77.5% (A/H1N1), 71.5% (A/H3N2), 58.1% (B/Victoria), and 61.7% (B/Yamagata). The reactogenicity and safety profile of QIV was consistent with TIV.

Conclusions: QIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens. The additional antigen did not appear to alter the safety profile of QIV compared with TIV. This suggests that the candidate QIV is a viable alternative to TIV for use in adults, and could potentially improve protection against influenza B.

Trial registration: Clinical Trials.gov: NCT01204671/114269.

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Related in: MedlinePlus

Solicited adverse events (total vaccinated cohort). Footnote: (A). local adverse events, (B). general adverse events. CI, confidence interval; GI, gastrointestinal; QIV, Inactivated quadrivalent influenza vaccine; TIV-Vic, inactivated trivalent influenza vaccine Victoria lineage B strain; TIV-Yam, inactivated trivalent influenza vaccine Yamagata lineage B strain.
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Figure 4: Solicited adverse events (total vaccinated cohort). Footnote: (A). local adverse events, (B). general adverse events. CI, confidence interval; GI, gastrointestinal; QIV, Inactivated quadrivalent influenza vaccine; TIV-Vic, inactivated trivalent influenza vaccine Victoria lineage B strain; TIV-Yam, inactivated trivalent influenza vaccine Yamagata lineage B strain.

Mentions: Reactogenicity during the 7-day post-vaccination period is shown in Figure 4. Injection site pain was the most frequent local symptom, and was reported by 36.4%, 36.8% and 31.3% of the QIV, TIV-Vic, and TIV-Yam groups respectively. Grade 3 solicited injection site symptoms were reported for ≤ 1.2% of subjects in any group. In the QIV, TIV-Vic and TIV-Yam groups, the most frequent general symptoms were fatigue (15.8%, 18.4% and 14.8%, respectively), headache (15.9%, 16.4% and 13.2%, respectively) and muscle ache (16.4%, 19.4% and 16.1%, respectively). Grade 3 solicited general symptoms were reported in < 1.0% of subjects in any group.


Immunogenicity, reactogenicity and safety of an inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine: a phase III, randomized trial in adults aged ≥18 years.

Kieninger D, Sheldon E, Lin WY, Yu CJ, Bayas JM, Gabor JJ, Esen M, Fernandez Roure JL, Narejos Perez S, Alvarez Sanchez C, Feng Y, Claeys C, Peeters M, Innis BL, Jain V - BMC Infect. Dis. (2013)

Solicited adverse events (total vaccinated cohort). Footnote: (A). local adverse events, (B). general adverse events. CI, confidence interval; GI, gastrointestinal; QIV, Inactivated quadrivalent influenza vaccine; TIV-Vic, inactivated trivalent influenza vaccine Victoria lineage B strain; TIV-Yam, inactivated trivalent influenza vaccine Yamagata lineage B strain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750613&req=5

Figure 4: Solicited adverse events (total vaccinated cohort). Footnote: (A). local adverse events, (B). general adverse events. CI, confidence interval; GI, gastrointestinal; QIV, Inactivated quadrivalent influenza vaccine; TIV-Vic, inactivated trivalent influenza vaccine Victoria lineage B strain; TIV-Yam, inactivated trivalent influenza vaccine Yamagata lineage B strain.
Mentions: Reactogenicity during the 7-day post-vaccination period is shown in Figure 4. Injection site pain was the most frequent local symptom, and was reported by 36.4%, 36.8% and 31.3% of the QIV, TIV-Vic, and TIV-Yam groups respectively. Grade 3 solicited injection site symptoms were reported for ≤ 1.2% of subjects in any group. In the QIV, TIV-Vic and TIV-Yam groups, the most frequent general symptoms were fatigue (15.8%, 18.4% and 14.8%, respectively), headache (15.9%, 16.4% and 13.2%, respectively) and muscle ache (16.4%, 19.4% and 16.1%, respectively). Grade 3 solicited general symptoms were reported in < 1.0% of subjects in any group.

Bottom Line: This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection.For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%.QIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Two antigenically distinct influenza B lineages have co-circulated since the 1980s, yet inactivated trivalent influenza vaccines (TIVs) include strains of influenza A/H1N1, A/H3N2, and only one influenza B from either the Victoria or Yamagata lineage. This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection. Formulations including both influenza B lineages could improve protection against circulating influenza B viruses. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in adults in stable health.

Methods: A total of 4659 adults were randomized 5:5:5:5:3 to receive one dose of QIV (one of three lots) or a TIV containing either a B/Victoria or B/Yamagata strain. Hemagglutination-inhibition assays were performed pre-vaccination and 21-days after vaccination. Lot-to-lot consistency of QIV was assessed based on geometric mean titers (GMT). For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%. Reactogenicity and safety profile of each vaccine were assessed. Clinicaltrials.gov: NCT01204671.

Results: Consistent immunogenicity was demonstrated for the three QIV lots. QIV was non-inferior to TIV for the shared vaccine strains, and was superior for the added alternate-lineage B strains. QIV elicited robust immune responses against all four vaccine strains; the seroconversion rates were 77.5% (A/H1N1), 71.5% (A/H3N2), 58.1% (B/Victoria), and 61.7% (B/Yamagata). The reactogenicity and safety profile of QIV was consistent with TIV.

Conclusions: QIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens. The additional antigen did not appear to alter the safety profile of QIV compared with TIV. This suggests that the candidate QIV is a viable alternative to TIV for use in adults, and could potentially improve protection against influenza B.

Trial registration: Clinical Trials.gov: NCT01204671/114269.

Show MeSH
Related in: MedlinePlus