Vaccine effectiveness of recombinant and standard dose influenza vaccines against influenza related hospitalization using a retrospective test-negative design.

BACKGROUND: Relative effectiveness of various vaccine formulations provide important input for vaccine policy decisions and provider purchasing decisions. We used electronic databases to conduct a test-negative case control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine (RIV4) compared with standard dose vaccines (SD-IIV4) against influenza hospitalization. METHODS: Adults 18-64 and ≥65 years of age hospitalized in a large U.S. health system (19 hospitals) in 2018-2019 and 2019-2020 who were clinically tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays were included. The hospital system electronic medical record (EMR) and the state immunization registry were used to confirm influenza vaccination. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. RESULTS: Of the 14,590 individuals included in the primary analysis, 3,338 were vaccinated with RIV4 and 976 were vaccinated with SD-IIV4, with the balance of 10,276 being unvaccinated. Most participants were white (80 %), most (70 %) had a high-risk condition, just over half were female (54 %) and age 65 years or older (53 %). Overall RIV4 rVE was significant when adjusted for propensity scores with inverse probability weights (rVE = 31; 95 % CI = 11 %, 46 %). Among younger adults (18-64 years-old), overall rVE of RIV4 was significant (rVE = 29; 95 % CI = 4 %, 47 %). CONCLUSIONS: Over all adults, both RIV4 and SD-IIV4 were effective against influenza hospitalization, with RIV4 providing better protection compared with SD-IIV4 overall, for females, younger adults, and those with no high-risk conditions.

Factors associated with humoral immune response in older adults who received egg-free influenza vaccine.

BACKGROUND: Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. METHODS: Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018-2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. RESULTS: Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). CONCLUSION: Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.

Cost-effectiveness of revised US pneumococcal vaccination recommendations in underserved minority adults < 65-years-old.

BACKGROUND: The 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recently recommended for US adults, giving either PCV20 alone or PCV15 followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) to all 65 + -year-olds and to high-risk younger adults. However, general population recommendations to vaccinate all 50-year-olds could reduce racial pneumococcal disease disparities given greater risk in underserved minority populations. METHODS: A Markov model examining hypothetical 50-year-old Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts estimated the incremental cost effectiveness of US adult pneumococcal vaccination recommendations compared to PCV20 or PCV15/PPSV23 for all 50-year-olds with no vaccination thereafter, or PCV20 or PCV15/PPSV23 for all at ages 50 and 65 years (50/65). Model parameters came from US databases, clinical trials, and Delphi panels. Cohorts were followed over their lifetimes from a healthcare perspective discounted at 3 %/year. RESULTS: PCV15/PPSV23 given at ages 50/65 had greatest public health impact. In Black cohorts, PCV15/PPSV23 at age 50 cost $104,723/quality adjusted life year (QALY) gained compared to PCV20 at age 50, while PCV15/PPSV23 at 50/65 cost $240,952/QALY gained compared to PCV15/PPSV23 at age 50. Both current recommendation options were more expensive and less effective than other strategies in both cohorts. In sensitivity analyses, age-based PCV20 or PCV15/PPSV23 use at ages 50 or 50/65 could be favorable depending on vaccine effectiveness or differential vaccine uptake, while current recommendations remained unfavorable. CONCLUSION: Recent risk-based US adult pneumococcal vaccination recommendations for adults < 65-years-old, were economically and clinically unfavorable compared to general population vaccination of all 50-year-olds in Black and non-Black cohorts. An age-based pneumococcal vaccination recommendation at age 50 years may reduce inequities in pneumococcal disease burden.

A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults.

BACKGROUND: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. METHODS: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. RESULTS: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. CONCLUSION: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.

Cost Effectiveness of Influenza Vaccine Choices in Children Aged 2-8 Years in the U.S.

INTRODUCTION: Prior evidence found live attenuated influenza vaccine (LAIV) more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, leading CDC in 2014 to prefer LAIV use in this group. However, since 2013, LAIV has not proven superior, leading CDC in 2015 to rescind their LAIV preference statement. Here, the cost effectiveness of preferred LAIV use compared with IIV in children aged 2-8 years is estimated. METHODS: A Markov model estimated vaccination strategy cost effectiveness in terms of cost per quality-adjusted life-year gained. Base case assumptions were equal vaccine uptake; IIV use when LAIV was not indicated (in 11.7% of the cohort); and no indirect vaccination effects. Sensitivity analyses included estimates of indirect effects from both equation- and agent-based models. Analyses were performed in 2014-2015. RESULTS: Using prior effectiveness data in children aged 2-8 years (LAIV=83%, IIV=64%), preferred LAIV use was less costly and more effective than IIV (dominant), with results sensitive only to LAIV and IIV effectiveness variation. Using 2014-2015 U.S. effectiveness data (LAIV=0%, IIV=15%), IIV was dominant. In two-way sensitivity analyses, LAIV use was cost saving over the entire range of IIV effectiveness (0%-81%) when absolute LAIV effectiveness was >7.1% higher than IIV, but never cost saving when absolute LAIV effectiveness was <3.5% higher than IIV. CONCLUSIONS: Results support CDC's decision to no longer prefer LAIV use and provide guidance on effectiveness differences between influenza vaccines that might lead to preferential LAIV recommendation for children aged 2-8 years.