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Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses. New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine., Author(s): Raffael Nachbagauer [sup.1] [sup.15] , Jodi Feser [sup.2] , Abdollah Naficy [sup.2] , David I. Bernstein [sup.3] [sup.4] , Jeffrey Guptill [sup.5] , Emmanuel B. Walter [sup.5] [sup.6] , [...]

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage., Author(s): Jill E. Fuller[sup.1] , Emmanuel B. Walter[sup.2] , Nancy Dole[sup.3] , Richard O'Hara[sup.3] , Amy H. Herring[sup.4] , Maureen S. Durkin[sup.5] , Bonny Specker[sup.6] , Betty Wey[sup.6] Author Affiliations: [...]

Background. Trivalent inactivated influenza vaccine (TIV) is recommended for all children ages 6 to 23 months. Delivering 2 doses of TIV at least 4 weeks apart to young children receiving this vaccine for the first time is challenging. Methods. We compared the immunogenicity and reactogenicity of the standard 2-dose regimen of TIV administered in the fall with an early schedule of a single spring dose followed by a fall dose of the same vaccine in healthy toddlers 6 to 23 months of age. Children were recruited in the spring to be randomized into either the standard or early schedule. An additional group was also enrolled in the fall as part of a nonrandomized standard comparison group. The 2002-2003 licensed TIV was administered in the spring; the fall 2003-2004 vaccine contained the same 3 antigenic components. Reactogenicity was assessed by parental diaries and telephone surveillance. Blood was obtained after the second dose of TIV for all children. The primary outcome measure was antibody response to influenza A/HIN1, A/H3N2, and B after 2 doses of vaccine, as determined by hemagglutination-inhibition titers [greater than or equal to] 1:32 and geometric mean titer (GMT). Results. Two hundred nineteen children were randomized to receive either the standard or early TIV schedule; 40 additional children were enrolled in the fall in the nonrandomized standard group. Response rates in the combined standard versus early groups were similar overall: 78% (GMT: 48) vs 76% (GMT: 57) to HIN1, 89% (GMT: 115) vs 88% (GMT: 129) to H3N2, and 52% (GMT: 24) vs 60% (GMT: 28) to B. Reactogenicity after TIV in both groups of children was minimal and did not differ by dose, age, or time between doses. Reaction rates were higher in those receiving TIV and concomitant vaccines compared with those receiving TIV alone. Overall rates of fever >38[degrees]C axillary and injection-site pain, redness, or swelling were 5.4%, 3.1%, 0.9%, and 1.1%, respectively. Conclusions. When the spring and fall influenza vaccines had the same 3 antigenic components, the early vaccine schedule resulted in similar immunogenicity and reactogenicity compared with the standard schedule. When the vaccine components do not change between years, initiating influenza vaccine in the spring at the time of routine office visits would facilitate full immunization of children against influenza earlier in the season. Pediatrics 2005;115:1039-1047; inactivated influenza vaccine, children., ABBREVIATIONS. TIV, trivalent inactivated influenza vaccine; CI, confidence interval; HAI, hemagglutination-inhibition; GMT, geometric mean titer. Trivalent inactivated influenza vaccine (TIV) has been demonstrated to be safe and effective in children [...]

This article compares the birth weights of infants born to HIV positive and negative mothers who engage in similar levels of high risk behavior such as drug use and unsafe sex. Results indicate that HIV positive women are significantly more likely to have babies with low birth weight.

Objectives. We determined rates of prenatal HIV testing and investigated barriers to testing. Methods. We surveyed 1362 representative parturient women from 7 hospitals in 4 locations of the United States. Results. Overall, 89.9% of women reported being offered HIV testing and 69.6% reported being tested. Proportions of women not offered testing differed by location (range = 5.2%-16.3%), as did proportions not tested (range = 12:2%-54,4%). Among women who perceived that their clinicians had not recommended testing, 41.7% were tested, compared with 92.8% of women who perceived a strong recommendation (P [is less than] .05). Private insurance for prenatal care was also associated with not being tested. Women gave multiple reasons for not being tested, most commonly not being at risk, having been tested recently, and the test's not being offered or recommended, cited by 55.3%. 39.1% and 11.1% of women, respectively, Conclusions. Although most parturient women were offered a prenatal HIV test and got tested testing proportions did not reach national goals and differed significantly by location and payment status. Concern about testing consequences was not a major barrier. Perception of clinicians' recommendations strongly influenced testing. Changing provider practices will be essential to implementing universal prenatal HIV testing. (Am J Public Health. 2001;91: 727-733)

OBJECTIVE. Children [greater than or equal to] 6 months of age who have previously received 1 dose of trivalent inactivated influenza vaccine are recommended to be given an additional single trivalent inactivated influenza vaccine dose the following fall. Limited data exist documenting the immunogenicity of 2 doses of influenza vaccine given in separate years to young children, and it is not known if the antigen content of each of the 2 doses of vaccine must be identical or similar to optimally immunize children in this age group. In 2004, the A/H3N2 and B antigens contained in trivalent inactivated influenza vaccine were changed from those in the 2003-2004 influenza vaccine, providing the opportunity to assess the effect of such a change on the single-dose recommendation in trivalent inactivated influenza vaccine-experienced toddlers. PATIENTS AND METHODS. We conducted an observational, nonrandomized, open-label study comparing immunogenicity and reactogenicity of 2 doses of trivalent inactivated influenza vaccine in 2 groups of healthy children aged 6 to 23 months. Children who had received 1 dose of 2003 trivalent inactivated influenza vaccine the previous season received 1 dose of 2004 trivalent inactivated influenza vaccine according to current guidelines (group 1). Trivalent inactivated influenza vaccine-naive toddlers received the standard 2 doses of 2004 trivalent inactivated influenza vaccine 1 month apart (group 2). Blood was obtained 4 weeks after the second dose of trivalent inactivated influenza vaccine. The primary outcome measure was antibody response to the 3 vaccine antigens in the 2004 trivalent inactivated influenza vaccine after 2 doses of vaccine, as determined by hemagglutination-inhibition antibody titers. Noninferiority of the antibody response was based on the proportion of subjects in each group achieving a titer of [greater than or equal to] 1:32 postvaccination to antigens (H1N1, H3N2, and B) contained in the 2004-2005 vaccine. For each antigen, the antibody response was proposed to be noninferior if the upper bound of the 95% confidence interval of the difference between the proportion of children in the 2 groups with postvaccination titers [greater than or equal to] 1:32 was RESULTS. Fifty six of 58 previously immunized children (group 1) and 63 of 64 vaccine-naive children (group 2) completed the study. The groups were similar, except group 1 was older at receipt of the second trivalent inactivated influenza vaccine. Reactogenicity did not differ by age or time between doses. Antibody responses to the unchanged influenza A/H1N1 antigen at 4 weeks after the second trivalent inactivated influenza vaccine dose were similar in both groups, with good responses as measured by geometric mean titer (75.2 vs 69.1) and percentage with antibody titers [greater than or equal to] 1:32 (82.1% group 1 vs 85.7% group 2). For the A/H3N2 antigen, which changed between 2003 and 2004, there was a significantly higher geometric mean titer in group 1 compared with group 2 (156 vs 53.7), but both groups had very high rates of seroconversion that were not statistically different (91% vs 84%). The antibody response to influenza B was significantly lower in group 1 recipients, who received only a single dose of 2005 vaccine, as measured by both geometric mean titer and percentage with antibody [greater than or equal to] 1:32. The group 1 geometric mean titer was 13.8, and the group 2 geometric mean titer was 49.1. Only 27% of children in group 1 achieved antibody levels [greater than or equal to] 1:32 to influenza B compared with 86% in group 2. Using logistic regression, we also determined that older children had less potentially seroprotective levels to influenza B. Overall, noninferiority of the antibody response for group 1 compared with group 2 was confirmed for influenza A/H3N2, was marginally significant for A/H1N1, and was not confirmed for influenza B. CONCLUSIONS. The assessment of immune responses in children after changes in vaccine composition is important, because influenza vaccines change frequently, affecting not only antibody responses in partially immunized toddlers, but potentially immune responses in more fully immunized individuals. In this study, a change in 2 different vaccine antigens enabled us to assess and compare the impact of the original priming antigens after relatively minor changes in 1 antigen (A/H3N2) or after considerable antigenic changes in another vaccine antigen (B). Our subjects demonstrated relatively good responses to the vaccine antigen change characterized by relatively minor changes (A/H3N2). Circulating virus may have primed infants in both groups to antigen more closely related to the 2004 influenza A/H3N2 strain. The high A/H3N2 antibody response to the second dose of trivalent inactivated influenza vaccine in children who were immunized the previous fall with a different vaccine is consistent with the fact that more children in group 1 were alive during this epidemic and, therefore, were more likely to have experienced priming with natural infection. In contrast, a decreased antibody response to the influenza B antigen was seen in children primed with the earlier 2003 vaccine, suggesting that the major change in B virus lineage in the 2004 vaccine reduced the priming benefit of previous vaccination. Our findings are reminiscent of antibody responses in children seen after immunization with different but novel influenza antigens, such as swine flu vaccine (influenza A/swine/ 1976/37-like virus). Our results should be taken into account when evaluating new vaccines in young children for novel viruses, such as new pandemic strains of influenza. The need for multiple doses of vaccine to produce potentially protective antibody levels in children needs to be considered, even when vaccine is in short supply. KEY WORDS. trivalent inactivated influenza vaccine, children, immunogenicity, reactogenicity., Janet A. Englund, MD, Emmanuel B. Walter, MD, MPH, Adepeju Gbadebo, MS, Arnold S. Monto, MD, Yuwei Zhu, MD, MS, Kathleen M. Neuzil, MD, [...]

OBJECTIVES. Immunoprophylaxis with influenza vaccine is the primary method for reducing the effect of influenza on children, and inactivated influenza vaccine has been shown to be safe and effective in children. The Advisory Committee on Immunization Practices recommends that children 6 to 23 months of age who are receiving trivalent inactivated influenza vaccine for the first time be given 2 doses; however, delivering 2 doses of trivalent inactivated influenza vaccine [greater than or equal to] 4 weeks apart each fall can be logistically challenging. We evaluated an alternate spring dosing schedule to assess whether a spring dose of trivalent inactivated influenza vaccine was capable of "priming" the immune response to a fall dose of trivalent inactivated influenza vaccine containing 2 different antigens. PATIENTS AND METHODS. Healthy children born between November 1, 2002, and December 31, 2003, were recruited in the spring and randomly assigned to either the alternate spring schedule or standard fall schedule. The 2003-2004 licensed trivalent inactivated influenza vaccine was administered in the spring; the fall 2004-2005 vaccine had the same A/H1N1 antigen but contained drifted A/H3N2 antigen and B antigen with a major change in strain lineage. Reactogenicity was assessed by parental diaries and telephone surveillance. Blood was obtained after the second dose of trivalent inactivated influenza vaccine for all of the children and after the first dose of trivalent inactivated influenza vaccine in the fall group. The primary outcome of this study was to demonstrate noninferiority of the antibody response after a spring-fall dosing schedule compared with the standard fall dosing schedule. Noninferiority was based on the proportion of subjects in each group achieving a hemagglutination-inhibition antibody titer of [greater than or equal to] 1:32 after vaccination to 2 of the 3 antigens (H1N2, H3N2, and B) contained in the 2004-2005 vaccine. For each antigen, the antibody response was proposed to be noninferior if, within the upper bound of 95% confidence interval, there was RESULTS. A total of 468 children were randomly assigned to either the spring (n = 233) or fall (n = 235) trivalent inactivated influenza vaccine schedule. Excellent response rates to A/H1N1, as measured by antibody levels [greater than or equal to] 1:32, were noted in both the spring (86%) and fall groups (93%). The A/H1N1 response rate of the spring group was noninferior to that of the fall group. Noninferiority of the spring schedule was not met with respect to the other 2 influenza antigens: for A/H3N2 the response was 70% in the spring group versus 83% for the fall group, and the response to B was 39% in the spring group versus 88% for the fall group. After 2 doses of vaccine, the geometric mean antibody titers also were less robust in the spring group for both A/H3N2 and B antigens. For each of the 3 vaccine antigens, the respective geometric mean antibody titers for the spring group versus the fall group were: A/H1N1, 79.5 [+ or -] 3.3 and 91.9 [+ or -] 2.6; A/H3N2, 57.1 [+ or -] 4.1 and 77.8 [+ or -] 3.7; and B, 18.0 [+ or -] 2.4 and 61.6 [+ or -] 2.5. However, a significantly higher proportion of children in the spring group achieved potentially protective levels of antibody to all 3 antigens after their first fall dose of trivalent inactivated influenza vaccine than children in the fall group after receiving their first fall dose. For influenza A/H1N1, there was an antibody level [greater than or equal to] 1:32 in 86% of children in the spring group versus 55% of children in the fall group. Likewise, for influenza A/H3N2, 70% of children in the spring group and 47% of children in the fall group had antibody levels > 1:32; for influenza B, the proportions were 39% of children in the spring group and 16% of children in the fall group. Reactogenicity after trivalent inactivated influenza vaccine in both groups of children was minimal and did not differ by dose. CONCLUSIONS. Although the immune response to the identical A/H1N1 vaccine antigen was similar in both groups, priming with different A/H3N2 antigens and B antigens in the spring produced a lower immune response to both antigens than that shown in children who received 2 doses of the same vaccine in the fall. However, ~70% of children in the spring group had a protective response to the H3N2 antigen after 2 doses. Initiating influenza immunization in the spring was superior to 1 dose of trivalent inactivated influenza vaccine in the fall. The goal of delivering 2 doses of influenza vaccine a month apart to vaccine-naive children within the narrow flu vaccination season is a challenge not yet met; thus far, only about half of children aged 6 to 23 months of age are receiving influenza vaccine. By using the spring schedule, we were able to administer 2 doses of trivalent inactivated influenza vaccine to a higher proportion of children earlier in the influenza vaccination season. In years when there is an ample supply of trivalent inactivated influenza vaccine, and vaccine remains at the end of the season, priming influenza vaccine-naive infants with a spring dose will lead to the earlier protection of a higher proportion of infants in the fall. This strategy may be particularly advantageous when there is an early start to an influenza season as occurred in the fall of 2003. A priming dose of influenza vaccine in the spring may also offer other advantages. Many vaccine-naive children may miss the second dose of fall trivalent inactivated influenza vaccine because of vaccine shortages or for other reasons, such as the potential implementation of new antigens at a late date. Even with seasonal changes in influenza vaccine antigens, by giving a springtime dose of trivalent inactivated influenza vaccine, such children would be more protected against influenza than would children who were only able to receive 1 dose in the fall. In summary, our data suggest that identical influenza antigens are not necessary for priming vaccine-naive children and that innovative uses of influenza vaccine, such as a springtime dose of vaccine, could assist in earlier and more complete immunization of young children. KEY WORDS. inactivated influenza vaccine, children, immunogenicity., Emmanuel B. Walter, MD, MPH, Kathleen M. Neuzil, MD, MPH, Yuwei Zhu, MD, MS, Mary P. Fairchok, MD, Martha E. Gagliano, MD, Arnold S. Monto, MD, Janet A. Englund, [...]