Factors associated with COVID-19 vaccination during June–October 2021: A multi-site prospective study

IntroductionVaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership.MethodsIn June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analyses assessed predictors of subsequent vaccination among those initially unvaccinated.ResultsIn June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9 %) became vaccinated by October 31, 2021. In June, unvaccinated participants were less likely to feel “very concerned” about getting COVID-19 than vaccinated participants (10.6 % vs. 43.3 %, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5 % reported vaccination before study end. Two latent factors predicted subsequent vaccination—being ‘more receptive’ was derived from motivation to protect one’s own or others’ health and resume usual activities; being ‘less receptive’ was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention.ConclusionThis study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions.     

Characteristics and incidence of vaccine adverse events after Bacille Calmette–Guérin vaccination: A national surveillance study in Japan from 2013 to 2017

BackgroundJapan amended the recommended age for the Bacille Calmette–Guérin (BCG) vaccination to less than 6 months after 2005, but subsequently amended the recommended age to 5–8 months (latest amendment, <1 year) in April 2013 due to the increasing incidence of BCG-associated osteitis/osteomyelitis since 2005.MethodsWe collected data on BCG-associated vaccine adverse events (VAEs) in the population aged <1 year between April 2013 and March 2017. The incidence of BCG-associated VAE was analyzed using census and vaccine coverage data from the government website. We compared the incidence of VAEs in patients vaccinated at less than 6 months with those vaccinated at 6 months or older.ResultsAmong the 581 BCG-associated VAEs recorded during the study period, 354 (61%) were male, and the average age at vaccination was 5.7 months. The incidence of VAEs per million population aged <1 year at vaccination was highest for suppurative lymphadenitis (63.7), followed by skin lesions (38.4), and BCG-associated osteitis/osteomyelitis (3.1). Disseminated BCG and anaphylaxis were rare (1.1 and 1.6%, respectively). The incidence of VAEs in the population vaccinated at <6 months of age was higher for BCG-associated osteitis/osteomyelitis (3.8) and disseminated BCG (1.3) than in the population vaccinated at ≥6 months.ConclusionsThe population vaccinated at <6 months of age was more likely to develop BCG-associated osteitis/osteomyelitis than the population vaccinated at ≥6 months of age, indicating that the change in the recommended vaccination age in 2013 might have contributed to the subsequent decrease in the incidence of BCG-associated osteitis/osteomyelitis.     

CD8+ T cells induced by adenovirus-vectored vaccine are capable of preventing establishment of latent murine γ-herpesvirus 68 infection

CD8+ T cells are known to control infections, but their role in preventing latent infection from establishing has not been thoroughly investigated.We hypothesized that a potent CD8+ T cell response patrolling the mucosal viral entry points could kill the first infected cells and thereby abrogate the infection before latency is established.To investigate this, replication deficient adenovirus serotype 5 vectors encoding murine γ-herpesvirus-68 CD8+ T cell epitopes linked to the T cell adjuvant Invariant chain, were developed. We show that intranasal vaccination of mice reduces the risk of establishment of latent infection from multiple intranasal ID50 challenges with murine γ-herpesvirus-68 by 81% per exposure at 14 days post vaccination. Protection waned over time, but immune responses were extended by heterologous prime-boost vaccination applied simultaneously intramuscularly and intranasally, and animals vaccinated 66 days prior to challenge showed a strong trend of long-term protection.Our data provides evidence that CD8+ T cells are able to protect against establishment of latent infection. Although the protective efficacy is difficult to maintain over time, this proof-of-concept study suggests a role for a CD8+ T cell arm in future vaccine strategies against latent human viral infections caused by pathogens such as HIV and multiple herpes virus.     

Where are children ages 5–17 years receiving their COVID-19 vaccinations? Variations over time and by sociodemographic characteristics,United States

BackgroundKnowing the settings where children ages 5–17 years received COVID-19 vaccination in the United States, and how settings changed over time and varied by socio-demographics, is of interest for planning and implementing vaccination programs.MethodsData from the National Immunization Survey-Child COVID-19 Module (NIS-CCM) were analyzed to assess place of COVID-19 vaccination among vaccinated children ages 5–17 years. Interviews from July 2021 thru May 2022 were included in the analyses for a total of n = 39,286 vaccinated children. The percentage of children receiving their COVID-19 vaccine at each type of setting was calculated overall, by sociodemographic characteristics, and by month of receipt of COVID-19 vaccine.ResultsAmong vaccinated children ages 5–11 years, 46.9 % were vaccinated at a medical place, 37.1 % at a pharmacy, 8.1 % at a school, 4.7 % at a mass vaccination site, and 3.2 % at some other non-medical place. Among vaccinated children ages 12–17 years, 35.1 % were vaccinated at a medical place, 47.9 % at a pharmacy, 8.3 % at a mass vaccination site, 4.8 % at a school, and 4.0 % at some other non-medical place. The place varied by time among children ages 12–17 years but minimally for children ages 5–11 years. There was variability in the place of COVID-19 vaccination by age, race/ethnicity, health insurance, urbanicity, and region.ConclusionChildren ages 5–17 years predominantly received their COVID-19 vaccinations at pharmacies and medical places. The large proportion of vaccinated children receiving vaccination at pharmacies is indicative of the success in the United States of expanding the available settings where children could be vaccinated. Medical places continue to play a large role in vaccinating children, especially younger children, and should continue to stock COVID-19 vaccine to keep it available for those who are not yet vaccinated, including the newly recommended group of children < 5 years.     

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

Typical time courses and appearance of skin reactions at the site of Bacillus Calmette-Guérin vaccination for infants inoculated at 5–8 months of age

BackgroundTaiwan increased the Bacillus Calmette-Guerin (BCG) vaccination age from 24 h after birth to 5–8 months of age to lower BCG-related osteitis/osteomyelitis in 2016. However, the sequences of skin changes at the injection site and in the corresponding lymph nodes are unknown for infants vaccinated at an older age.MethodsWe prospectively collected the photographs of skin reactions within 6 months after vaccination. The type, size, onset time, and duration of the skin reactions were recorded and analyzed.ResultsWe enrolled 532 infants. The types and median times at onset of skin reactions were as follows: erythema at week 1, induration at week 3, ecchymosis at week 4, and ulceration at week 6. The peak skin responses were at week 6, with average sizes of 8.4 mm, 7.4 mm, and 8.2 mm for erythema, induration, and ecchymosis, respectively. The duration of induration was long, with 57.6 % and 23 % of the infants still having a response at week 12 and 24, respectively. The rate of induration size ≥ 20 mm was 1.7 % (95 % confidence interval: 0.8 %–3.2 %). Overall, 46.4 % of the infants experienced ulcerative change, with most occurring at week 6 (34.1 %), and 9.5 % and 4.1 % of the infants still had ulceration at week 12 and 16, respectively. Twelve infants (2.3 %) had spontaneous resolution of regional lymphadenitis, with the onset time ranging from week 1 to 12. All infants had developed a scar at the end of follow-up.ConclusionOur study demonstrates the typical appearance and time courses of skin reactions in infants who received the BCG vaccination at older than 5 months of age. Infants vaccinated at this age may have a more potent skin response with longer induration and ulceration than those vaccinated at birth.     

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes

BackgroundRecommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization.MethodsAfter eight years, we recontacted women who received two-dose of bivalent or three-dose—either bivalent or quadrivalent—, HPV vaccine when aged 9–10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups.ResultsThe prevalence of HPV16/18 types was 6.8% (95 %CI 3.2–14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2–5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0–7.0%) in the two-dose group (n = 0/51).ConclusionHPV vaccination, with two-dose of bivalent or three-dose schemes—either with the bivalent or quadrivalent vaccine—, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.     

Durable antibody responses elicited by 1 dose of Ad26.COV2.S and substantial increase after boosting: 2 randomized clinical trials

BackgroundAd26.COV2.S is a well-tolerated and effective vaccine against COVID-19. We evaluated durability of anti-SARS-CoV-2 antibodies elicited by single-dose Ad26.COV2.S and the impact of boosting.MethodsIn randomized, double-blind, placebo-controlled, phase 1/2a and phase 2 trials, participants received single-dose Ad26.COV2.S (5 × 10¹⁰ viral particles [vp]) followed by booster doses of 5 × 10¹⁰ vp or 1.25 × 10¹⁰ vp. Neutralizing antibody levels were determined by a virus neutralization assay (VNA) approximately 8–9 months after dose 1. Binding and neutralizing antibody levels were evaluated by an enzyme-linked immunosorbent assay and pseudotyped VNA 6 months after dose 1 and 7 and 28 days after boosting.ResultsData were analyzed from phase 1/2a participants enrolled from 22 July–18 December 2020 (Cohort 1a, 18–55 years [y], N = 25; Cohort 2a, 18–55y, N = 17; Cohort 3, ≥65y, N = 22), and phase 2 participants from 14 to 22 September 2020 (18–55y and ≥ 65y, N = 73). Single-dose Ad26.COV2.S elicited stable neutralizing antibodies for at least 8–9 months and stable binding antibodies for at least 6 months, irrespective of age. A 5 × 10¹⁰ vp 2-month booster dose increased binding antibodies by 4.9- to 6.2-fold 14 days post-boost versus 28 days after initial immunization. A 6-month booster elicited a steep and robust 9-fold increase in binding antibody levels 7 days post-boost. A 5.0-fold increase in neutralizing antibodies was observed by 28 days post-boost for the Beta variant. A 1.25 × 10¹⁰ vp 6-month booster elicited a 3.6-fold increase in binding antibody levels at 7 days post-boost versus pre-boost, with a similar magnitude of post-boost responses in both age groups.ConclusionsSingle-dose Ad26.COV2.S elicited durable antibody responses for at least 8 months and elicited immune memory. Booster-elicited binding and neutralizing antibody responses were rapid and robust, even with a quarter vaccine dose, and stronger with a longer interval since primary vaccination.Trial Registration: ClinicalTrials.gov Identifier: NCT04436276, NCT04535453.     

Duration of protection and humoral immunity induced by an adenovirus-vectored subunit vaccine for foot-and-mouth disease (FMD) in Holstein steers

Foot-and-mouth disease (FMD) is a highly contagious viral infection of cloven hooved animals that continues to cause economic disruption in both endemic countries or when introduced into a formally FMD free country. Vaccines that protect against clinical disease and virus shedding are critical to control FMD. The replication deficient human adenovirus serotype 5 (Ad5) vaccine vector expressing empty FMD virus (FMDV) capsid, AdtFMD, is a promising new vaccine platform. With no shedding or spreading of viral vector detected in field trials, this vaccine is very safe to manufacture, as there is no requirement for high containment faciitites. Here, we describe three studies assessing the proportion of animals protected from clinical vesicular disease (foot lesions) following live-FMDV challenge by intradermolingual inoculation at 6 or 9 months following a single vaccination with the commercial AdtFMD vaccine, provisionally licensed for cattle in the United States. Further, we tested the effect of vaccination route (transdermal, intramuscular, subcutaneous) on clinical outcome and humoral immunity. Results demonstrate that a single dose vaccination in cattle with the commercial vaccine vector expressing capsid proteins of the FMDV strain A24 Cruzeiro (Adt.A24), induced protection against clinical FMD at 6 months (100% transdermal, 80% intramuscular, and 60% subcutaneous) that waned by 9 months post-vaccination (33% transdermal and 20% intramuscular). Post-vaccination serum from immunized cattle (all studies) generally contained FMDV specific neutralizing antibodies by day 14. Anti-FMDV antibody secreting cells are detected in peripheral blood early following vaccination, but are absent after 28 days post-vaccination. Thus, the decay in antibody mediated immunity over time is likely a function of FMDV-specific antibody half-life. These data reveal the short time span of anti-FMDV antibody secreting cells (ASCs) and important performance characteristics of needle-free vaccination with a recombinant vectored subunit vaccine for FMDV.     

Effects of measles-containing vaccination in children with severe underlying neurologic disease

BackgroundMeasles outbreaks pose significant risk for those unvaccinated.Patients and methodsMeasles-containing vaccine was offered to unvaccinated children with severe neurologic diseases during a measles outbreak. Vaccination adverse events were reported by parents 30 days following vaccination. Long term effects were evaluated 12 months post vaccination.ResultsTwenty-seven children were vaccinated (36 doses given). Half of parents (51.8%) reported no adverse events following immunization. Adverse events included afebrile seizures (6/36), fever alone (5/36) and febrile seizures (5/36). Two children required hospitalization. Quadrivalent measles-containing vaccine combined with varicella was associated with febrile seizures (p = 0.04). No child needed adjustment of the anti-epileptic treatment or exhibited developmental regression.ConclusionIn a series of children with prior severe neurologic disease, the safety-tolerability profile of vaccines containing a measles vaccine component suggests that vaccination is justified. Main side effect was seizure aggravation in children with known epileptic disease.     

Duration of influenza vaccine effectiveness in the elderly in Japan: A retrospective cohort study using large-scale population-based registry data

BackgroundThe immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness.MethodsWe used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases).ResultsWe identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43–0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53–1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65–69 and 80-years, 5 months in 70–79 years.ConclusionsOur study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously.     

Trend in varicella patients 4 years after implementation of universal two-dose varicella vaccination in Japan

ObjectiveTo elucidate the trend and clinical spectrum of virologically diagnosed varicella patients after implementation of universal vaccination as a national immunization program in Japan.Patients and methodsStudy subjects were patients suspected of varicella, less than 15 years of age, who visited 14 pediatric clinics in the Nagoya VZV Study Group from September 2015 to August 2019. Practitioners collected patient samples and information such as backgrounds, clinical symptoms, and previous immunization status. All patients were confirmed as having varicella based on molecular diagnostic assays.ResultsVaricella zoster virus (VZV) DNA was detected in swab samples from 506 (83.1%) of the 609 suspected patients. The 455 varicella patients for whom vaccination status was available were divided into two groups: 180 universal vaccination targets and 275 non-targets. Numbers of monthly varicella patients decreased gradually during the observation period. In the 2016/17 season, the seasonal epidemic of varicella became undetectable in the universal vaccination target group, and starting in the 2017/18 season, it was obscured even in the non-target group. The median age of patients was significantly lower in the universal vaccination target group (3 years) than the non-target group (7 years) (P < 0.001). Vaccination status differed significantly between the two groups (P < 0.001). Most varicella patients were in the non-target group, especially those who had been vaccinated once (60.4%). Frequency of fever (P < 0.001) and number of skin rashes at the time of the first hospital visit (P = 0.001) were significantly higher in the non-target group.ConclusionsAlthough the number of childhood varicella patients declined after implementation of national immunization with two doses of varicella vaccination, sporadic outbreaks still occurred, mainly in the non–universal vaccination target group. Insufficient vaccination of members of this group is likely to be a major reason for small local outbreaks.     

Weaker protection against tuberculosis in BCG-vaccinated male 129 S2 mice compared to females

BCG – the only available vaccine against tuberculosis (TB) - was first given to babies 100 years ago in 1921. While it is effective against TB meningitis and disseminated TB, its efficacy against pulmonary TB is variable, notably in adults and adolescents. TB remains one of the world’s leading health problems, with a higher prevalence among men. Male sex is associated with increased susceptibility to Mycobacterium tuberculosis in mice, but sex-specific responses to BCG vaccination have not been examined. In this study we vaccinated TB-susceptible 129 S2 mice with BCG and challenged with low-dose M. tuberculosis H37Rv by aerosol infection. BCG was protective against TB in both sexes, as unvaccinated mice lost weight more rapidly than vaccinated ones and suffered from worse lung pathology. However, female mice were better protected than males, showing lower lung bacterial burdens and less weight loss. Overall, vaccinated female mice had increased numbers of T cells and less myeloid cells in the lungs compared to vaccinated males. Principal component analysis of measured features revealed that mice grouped according to timepoint, sex and vaccination status. The features that had the biggest impact on grouping overall included numbers of CD8 T cells, CD8 central memory T cells and CD4 T effector cells, with neutrophil and CD11b⁺GR-1⁻ cell numbers having a big impact at day 29. Hierarchical clustering confirmed that the main difference in global immune response was due to mouse sex, with only a few misgrouped mice. In conclusion, we found sex-specific differences in response to M. tuberculosis H37Rv -challenge in BCG-vaccinated 129 S2 mice. This highlights the need to include both male and female mice in preclinical testing of vaccine candidates.     

Use of protective antigen of Bacillus anthracis as a model recombinant antigen to evaluate toll-like receptors 2, 3, 4, 7 and 9 agonists in mice using established functional antibody assays,antigen-specific antibody assays and cellular assays

Toll-like receptor (TLR) agonists can act as immune stimulants alone or as part of alum or oil formulations. Humoral and cellular immune responses were utilized to assess quantitative and qualitative immune response enhancement by TLR agonists using recombinant protective antigen (rPA) of B. anthracis as a model antigen. To rPA, combined with aluminum hydroxide (Alhydrogel; Al(OH)3) or squalene (AddaVax?), was added one of 7 TLR agonists: TLR2 agonist Pam3CysSK4 (PamS), TLR3 agonist double stranded polyinosinic:polycytidylic acid (PolyIC), TLR4 agonists Monophosphoryl lipid A (MPLA) or glucopyranosyl lipid A (GLA), TLR7-8 agonists 3M?052 or Resiquimod (Resiq), or TLR9 agonist CPG 7909 (CPG). CD-1 or BALB/c mice received two intraperitoneal or intramuscular immunizations 14 days apart, followed by serum or spleen sampling 14 days later. All TLR agonists except PamS induced high levels of B. anthracis lethal toxin-neutralizing antibodies and immunoglobulin G (IgG) anti-PA. Some responses were >100-fold higher than those without a TLR agonist, and IP delivery (0.5 mL) induced higher TLR-mediated antibody response increases compared to IM delivery (0.05 mL). TLR7-8 and TLR9 agonists induced profound shifts of IgG anti-PA response to IgG2a or IgG2b. Compared to the 14-day immunization schedule, use of a shortened immunization schedule of only 7 days between prime and boost found that TLR9 agonist CPG in a squalene formulation maintained higher interferon-γ-positive cells than TLR4 agonist GLA. Variability in antibody responses was lower in BALB/c mice than CD-1 mice but antibody responses were higher in CD-1 mice. Lower serum 50% effective concentration (EC50) values were found for rPA-agonist formulations and squalene formulations compared to Al(OH)3 formulations. Lower EC50 values also were associated with low frequency detection of linear peptide epitopes. In summary, TLR agonists elicited cellular immune responses and markedly boosted humoral responses.     

Subcutaneous nodules following immunization in children; in Victoria,Australia from 2007 to 2016

BackgroundSubcutaneous nodules are a rare adverse event following immunization (AEFI). We aimed to describe nodules at the injection site reported to SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community) using the Brighton Collaboration Case Definition (BCCD), management and recurrence following subsequent immunizations.MethodWe assessed 58 cases (<18 years of age) of ‘nodule at injection site’ reported to SAEFVIC, Melbourne, Australia, between May 2007 and June 2016. Case details were analyzed from records and phone interview follow-up. The Australian Immunization Registry was reviewed for immunization status.Results71% (41/58 reported cases) were consistent with the BCCD for subcutaneous nodule, 14% (8 cases) were ‘possible subcutaneous nodules’, 10% (6 cases) were nodules associated with BCG immunization and 5% (3 cases) were attributable to an alternative diagnosis. The median age at immunization was 12 months, (range 1 month–12 years); 54% male (22/41 cases). 17% (7 cases) had multiple nodules. Nodules were associated with immunizations containing aluminum (74%, 36/49 nodules), no aluminum (8%, 4 nodules) and unknown (18%, 9 nodules). Most cases developed symptoms within 3 days post-immunization (59%, 24 cases) and in the thigh (59%, 29 nodules). Pruritus was associated in 41% (17 cases). Around 1/3 (34%) of nodules resolved 6 months post immunization, 2/3 (68%) by 12 months, however 1/4 (24%) remained persistent for >24 months. 5 cases had prior nodules and 1 case had recurrence with subsequent immunization. 83% (34 cases) were fully immunized for age at follow-up.ConclusionSubcutaneous nodules at the injection site may occur following a wide range of vaccines, including vaccines without aluminum. All cases require careful review and where possible, specialist management and to support subsequent immunizations.     

Impact of prior flavivirus vaccination on immunogenicity and efficacy of an inactivated Zika vaccine in Indian rhesus macaques

Flaviviruses are antigenically related. We evaluated the immunogenicity and efficacy of Takeda’s purified inactivated Zika vaccine (PIZV) candidate in macaques previously vaccinated with several commercially available heterologous flavivirus vaccines. Heterologous flavivirus vaccination did not elicit Zika virus (ZIKV) neutralizing antibodies and did not impact neutralizing antibody titers after one dose of PIZV. After a second PIZV dose previous vaccination with flavivirus vaccines had variable impact on ZIKV neutralizing antibody titers. However, all macaques were protected against viremia after Zika virus challenge 8–12 months post-PIZV vaccination. Therefore, vaccine-induced immunity against heterologous flavivirus vaccines does not impact PIZV efficacy in macaques.     

Human papillomavirus vaccination coverage among men who have sex with men—National HIV Behavioral Surveillance,United States, 2017

Men who have sex with men (MSM) are at high risk for infections and diseases caused by human papillomavirus (HPV), many of which are vaccine-preventable. In the United States, routine HPV vaccination has been recommended for adolescent males since 2011. This analysis evaluated self-reported receipt of ≥ 1 HPV vaccine dose by age group and HIV status among adult MSM using 2017 data from National HIV Behavioral Surveillance (NHBS) and compared the proportion vaccinated to prior years. Among 10,381 MSM aged ≥ 18 years, 17.9% of MSM overall and 28.4% of MSM living with HIV reported any HPV vaccination. Among 2,482 MSM aged 18–26 years, 32.8% overall and 51.3% living with HIV reported HPV vaccination. Since 2011, the proportion of MSM aged 18–26 years reporting HPV vaccination has increased over six-fold. As vaccinated adolescents age into young adults, coverage will continue to increase overall, including among MSM.     

COVID-19 vaccination coverage in patients with chronic obstructive pulmonary disease – A cross-sectional study in Hungary

IntroductionCoronavirus infection is a particular risk for patients with chronic obstructive pulmonary disease (COPD), because they are much more likely to become severely ill due to oxygen supply problems. Primary prevention, including COVID-19 vaccination is of paramount importance in this disease group. The aim of our study was to assess COVID-19 vaccination coverage in COPD patients during the first vaccination campaign of the COVID-19 pandemic.MethodsA cross-sectional observational study (CHANCE) has been conducted in COPD patients in the eastern, western and central regions of Hungary from 15th November 2021. The anthropometric, respiratory function test results and vaccination status of 1,511 randomly selected patients were recorded who were aged 35 years and older.ResultsThe median age was 67 (61–72) years, for men: 67 (62–73) and for women: 66 (60–72) years, with 47.98 % men and 52.02 % women in our sample. The prevalence of vaccination coverage for the first COVID-19 vaccine dose was 88.62 %, whereas 86.57 % of the patients received the second vaccine dose. When unvaccinated (n = 172) and double vaccinated (n = 1308) patients were compared, the difference was significant both in quality of life (CAT: 17 (12–23) vs 14 (10–19); p < 0.001) and severity of dyspnea (mMRC: 2 (2–2) vs 2 (1–2); p = 0.048). The COVID-19 infection rate between double vaccinated and unvaccinated patients was 1.61 % vs 22.67 %; p < 0.001 six months after vaccination. The difference between unvaccinated and vaccinated patients was significant (8.14 % vs 0.08 %; p < 0.001) among those with acute COVID-19 infection hospitalized. In terms of post-COVID symptoms, single or double vaccinated patients had significantly fewer outpatient hospital admissions than unvaccinated patients (7.56 vs 0 %; p < 0.001).ConclusionThe COVID-19 vaccination coverage was satisfactory in our sample. The uptake of COVID-19 vaccines by patients with COPD is of utmost importance because they are much more likely to develop severe complications.     

Prenatal tetanus-diphtheria-acellular pertussis vaccine effectiveness at preventing infant pertussis

ObjectiveTo evaluate the effectiveness of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine containing five pertussis components (Tdap5; Adacel®, Sanofi) when given during pregnancy at preventing pertussis in infants less than 2 months of age.MethodsThe US Centers for Disease Control and Prevention (CDC), in collaboration with the Emerging Infections Program (EIP) Network, undertook a case-control study evaluating the effectiveness of Tdap vaccination in pregnancy against pertussis in infants less than 2 months of age based on data collected by the EIP Network from 2011 through 2014. The dataset from the CDC/EIP Network study was used to conduct this product-specific vaccine effectiveness analysis of Tdap5 vaccination in pregnancy to prevent disease in young infants. The main outcome of interest was vaccine effectiveness in infants whose pregnant parents were vaccinated with Tdap5 between 27 and 36 weeks’ gestation, in accordance with the ideal timing for Tdap vaccination in pregnancy recommended by the US Advisory Committee on Immunization Practices. Odd ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression, and vaccine effectiveness was calculated as (1–OR) × 100 %.ResultsThere were 160 infant pertussis cases and 302 matched controls included in this Tdap5-specific study. Tdap5 effectiveness in preventing pertussis in infants whose pregnant parents were vaccinated between 27 and 36 weeks’ gestation was 92.5 % (95 % CI, 38.5 %–99.1 %). Effectiveness of Tdap5 against pertussis-related hospitalization in infants whose pregnant parents were vaccinated between 27 and 36 weeks’ gestation could not be calculated due to lack of discordance among matched cases and controls. Vaccination of the parents after pregnancy or less than 14 days before delivery did not protect infants from pertussis.ConclusionsTdap5 vaccination in pregnancy between 27 and 36 weeks’ gestation is highly effective at protecting young infants from pertussis.Study registration: ClinicalTrials.gov, NCT05040802.     

Impact of prior vaccination on antibody response and influenza-like illness among Australian healthcare workers after influenza vaccination in 2016

BackgroundEpidemiological studies suggest that influenza vaccine effectiveness decreases with repeated administration. We examined antibody responses to influenza vaccination among healthcare workers (HCWs) by prior vaccination history and determined the incidence of influenza infection.MethodsHCWs were vaccinated with the 2016 Southern Hemisphere quadrivalent influenza vaccine. Serum samples were collected pre-vaccination, 21–28 days and 7 months post-vaccination. Influenza antibody titres were measured at each time-point using the haemagglutination inhibition (HI) assay. Immunogenicity was compared by prior vaccination history.ResultsA total of 157 HCWs completed the study. The majority were frequently vaccinated, with only 5 reporting no prior vaccinations since 2011. Rises in titres for all vaccine strains among vaccine-naïve HCWs were significantly greater than rises observed for HCWs who received between 1 and 5 prior vaccinations (p < 0.001, respectively). Post-vaccination GMTs against influenza A but not B strains decreased as the number of prior vaccinations increased from 1 to 5. There was a significant decline in GMTs post-season for both B lineages. Sixty five (41%) HCWs reported at least one influenza-like illness episode, with 6 (4%) identified as influenza positive.ConclusionsVarying serological responses to influenza vaccination were observed among HCWs by prior vaccination history, with vaccine-naïve HCWs demonstrating greater post-vaccination responses against A(H3N2).