99. Immune Responses to Influenza Vaccines in Children and Young Adults

Abstract Background Immune responses to influenza vaccines (IV) are influenced by pre-existing antibodies to vaccine components. Immune responses to vaccines were evaluated following vaccination with quadrivalent egg-based live-attenuated influenza vaccine (LAIV4) and cell-culture inactivated influenza vaccine (ccIIV4). Methods Racially diverse (48.0% non-white), healthy, community-dwelling children and young adults aged 4-21 years (median, 18.3 years) were randomized 1:1 in blocks of 4 to receive intramuscular ccIIV4 (Flucelvax: n=100) or nasal LAIV4 (FluMist: n=98); baseline demographics were similar between groups. Blood was drawn at day 0 pre-vaccination and at day 28 (21-35 days) post vaccination. Hemagglutination inhibition (HI) assays against egg-grown A/H1N1, A/H3N2, both vaccine B/strains and cell-grown A/H3N2 antigens were conducted. Geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers were analyzed. Results Day 0 GMTs were similar for LAIV4 and ccIIV4. Day 28 GMTs were higher for ccIIV4 (p< 0.05) and increased following vaccination for all 5 antigens (p< 0.05) except B/Phuket following LAIV4. The GMFR range was 2.4 to 3.0 for ccIIV4 and 1.0 to 1.3 for LAIV4. In linear regression controlling for age and prior season vaccination for both vaccines, baseline titers inversely predicted GMFR. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar within vaccine type. Figure 1. Day 0 and Day 28 A(H1N1) titers for ccIIV4 Figure 2. Day 0 and Day 28 A(H1N1) titers for LAIV4 Conclusion The HI response to ccIIV4 was greater than LAIV4 in this study of mostly older children. Day 0 HI titers were 1) a significant determinant of GMFR; 2) the strongest predictors of day 28 GMFR; and 3) more highly correlated (negatively) with GMFR following ccIIV4 than LAIV4. For both IV, the GMFR for cell-grown and egg-grown A/H3N2 antigens did not differ within IV type. Future studies incorporating immunoglobulin and cellular immune responses may delineate differences between these IV types not observable through HI assays. Disclosures Mary Patricia Nowalk, PhD, Merck & Co., Inc. (Grant/Research Support) Richard K. Zimmerman, MA;MD;MPH;MS, Sanofi Pasteur (Research Grant or Support) Judith M. Martin, MD, Merck Sharp and Dohme (Consultant)

Background. Immune responses to influenza vaccines (IV) are influenced by pre-existing antibodies to vaccine components. Immune responses to vaccines were evaluated following vaccination with quadrivalent egg-based live-attenuated influenza vaccine (LAIV4) and cell-culture inactivated influenza vaccine (ccIIV4).
Results. Day 0 GMTs were similar for LAIV4 and ccIIV4. Day 28 GMTs were higher for ccIIV4 (p< 0.05) and increased following vaccination for all 5 antigens (p< 0.05) except B/Phuket following LAIV4. The GMFR range was 2.4 to 3.0 for ccIIV4 and 1.0 to 1.3 for LAIV4. In linear regression controlling for age and prior season vaccination for both vaccines, baseline titers inversely predicted GMFR. The GMFR to A/ H3N2 cell-grown and egg-grown antigens were similar within vaccine type. Day 0 and Day 28 A(H1N1) titers for LAIV4 Conclusion. The HI response to ccIIV4 was greater than LAIV4 in this study of mostly older children. Day 0 HI titers were 1) a significant determinant of GMFR; 2) the strongest predictors of day 28 GMFR; and 3) more highly correlated (negatively) with GMFR following ccIIV4 than LAIV4. For both IV, the GMFR for cell-grown and egg-grown A/H3N2 antigens did not differ within IV type. Future studies incorporating immunoglobulin and cellular immune responses may delineate differences between these IV types not observable through HI assays.
Disclosures Background. Measles, mumps and rubella (MMR) vaccine is a live-attenuated vaccine usually contraindicated within the first two years of hematopoietic cell transplant (HCT). During the 2019 measles outbreak at our center, the benefits of administering MMR vaccine within the first two years after HCT were weighed against the potential risks.
Methods. We conducted a retrospective review of patients who received MMR vaccination within two years of an autologous or allogeneic HCT. Patients' demographics, date and type of HCT, underlying hematologic disease, type of immunosuppressive therapy and date of MMR vaccination were extracted from the electronic medical record. Adverse reactions that could be related to the vaccine were collected for up to 42 days post-vaccination and all hospitalizations and deaths following vaccination were reviewed.
Results. A total of 129 patients (75 autologous and 54 allogeneic HCT) were vaccinated between 300-729 days after HCT (median of 718 days). The median age at vaccination was 61 years old, 57% of the patients were male and 43% were on immunosuppressive therapy, 87% of whom were on maintenance therapy for multiple myeloma after auto-HCT. Seven patients (5%) had adverse reactions within 42 days of vaccination: six had respiratory tract infections (three with associated fever) and one had a rash leading to a brief hospitalization. This was a 37-year-old female who had an allogeneic HCT 542 days prior to MMR vaccination. She presented with a centrifugal maculopapular rash that was confirmed to be caused by the vaccine strain rubella virus (Fig 1). She fully recovered without sequalae. There was no other vaccine-associated illness identified in the cohort, after a median follow-up of 676 days.

Conclusion
. MMR vaccine appears to be well tolerated in selected HCT recipients when given earlier than 2 years after transplant. No attributable severe outcomes or deaths were described. A mild uncomplicated case of vaccine-associated rubella illness was seen after vaccination. In the setting of a measles outbreak, assessment of potential risks and benefits of MMR vaccination given within two years of HCT remains important.

Session: O-21. Innovations and Advancements in Vaccines
Background. Existing disparities in vaccination rates across different social and demographic groups in the US may have been exacerbated during the Coronavirus Disease 2019 (COVID) pandemic, leaving some children at risk for vaccine-preventable diseases. This study examined sociodemographic and risk factors of PCV13 infant primary series vaccination completion, before and during COVID.
Methods. Retrospective data from the Optum's de-identified Clinformatics Data Mart Database were used to create 3 cohorts: C1, Pre-COVID; C2, During COVID; C3, Cross-COVID (Figure 1). C1 and C3 (C1&3) were combined and compared with C2 for primary dosing completion before and during COVID according to infant/caregiver characteristics. Full completion (FC) was defined as receipt of 3 doses of PCV13 within 8 months of birth. M ultivariable logistic regression was used to compare FC vs. partial completion or no vaccine. Descriptive analyses were used to compare FC before and during COVID within subgroups.

Figure 1: Study population and inclusion criteria
Results. A total of 132,183 and 16,522 infants with at least 8 months of follow up time were enrolled in C1&3 and C2, respectively. FC was significantly higher before COVID-19 (adjusted odds ratio = 1.12, 95% CI: 1.07-1.17). Adjusting for COVID, FC was significantly lower in infants who were Black, with co-morbidities or risk factors, living in households with >1 children or no children, household annual income < $99k, residing in a neighborhood with median education of high school or below, and whose primary caregiver was aged <25 years (Table 1). Comparing FC before and during COVID, the % decline relative to pre-COVID was > 2% among infants who were White, residing in the Mountain, New England or Pacific regions, in a household with 2 children, >$100k annual income, employer-based insurance or HMO, and median neighborhood education of bachelor degree plus (Table 2). Table 1. Multivariable binomial logistic regression results for PCV13 full primary dosing completion vs. not full completion (partial or no vaccine), N=144,799*