Sendai virus particles carrying target virus glycoproteins for antibody induction

Induction of antibodies targeting viral glycoproteins is a key for the development of a vaccine against enveloped virus infection. Glycoproteins on the virion exhibiting native multimer structure may be a good immunogen to present antibody epitopes, but it is often difficult to prepare immunogenic inactivated virions. Preparation of soluble glycoprotein multimers has been attempted, while virus-like particles carrying target glycoproteins can be a more immunogenic antigen. In the present study, a target glycoprotein-embedded Sendai virus (SeV) particle was developed for induction of anti-virus antibodies. We constructed a chimeric antigen, HIV-1 EnvF, consisting of HIV-1 Env ectodomain and SeV F transmembrane-cytoplasmic domain, which was shown to be efficiently incorporated into the SeV virion. EnvF was recognized by anti-HIV-1 broadly-neutralizing monoclonal antibodies (bnAbs) including 35O22 that targets an Env trimer-dependent epitope. Analysis revealed that HIV-1_AD8 EnvF can mediate viral entry into the cells, which is inhibited by anti-HIV-1 bnAbs and HIV-1 entry inhibitors, suggesting that the EnvF exhibits an HIV-1 Env native-like functional structure to present bnAb epitopes. Immunization of mice with replication-defective SeVs expressing HIV EnvF and non-infectious SeV particles (NVP) carrying HIV EnvF efficiently induced anti-HIV Env antibodies. HTLV-1 EnvF also showed the potential to efficiently induce anti-HTLV-1 Env antibodies. These results indicate that SeV particles carrying EnvF can be a promising vaccine platform for induction of antibodies targeting enveloped virus glycoproteins.     

Influenza vaccination hesitancy and its determinants among elderly in China: A national cross-sectional study

BackgroundThe Chinese elderly face a significant threat from seasonal influenza, owing to the consistently low vaccination coverage. This study investigated the prevalence and determinants of influenza vaccination hesitancy among the Chinese elderly.MethodsIn 2019, 3849 elderly individuals from 10 provinces in China were recruited in a cross-sectional survey. Multinomial logistic regression was applied to investigate the determinants of influenza vaccination hesitancy.ResultsAmong the elderly respondents, 37.18% expressed some degree of hesitancy towards influenza vaccination: 19.28% were hesitant, and 17.90% refused influenza vaccination, including 19.28% acceptors with doubts and 17.90% refusers. Only 39.10% of the respondents considered themselves as the priority group for influenza vaccination, and 13.93% reported receiving a recommendation for vaccination from healthcare workers. Respondents with higher education levels and from urban areas had significantly higher odds of vaccine hesitancy than their counterparts. Confidence in the safety of vaccines was negatively associated with vaccine hesitancy, but confidence in vaccine efficacy had no such association. Respondents who perceived themselves as highly susceptible to influenza (AOR = 0.85; 95 %CI = 0.77–0.93) and those aware of the elderly as a priority group for influenza vaccination (AOR = 0.51; 95 %CI = 0.41–0.64) had a significantly lower odds of being refusers.ConclusionThis study found a high prevalence of hesitancy towards influenza vaccination among the Chinese elderly, especially well-educated and urban-dwelling respondents. The government should address vaccine hesitancy through culturally appropriate communication, subsidies for vaccination, and actively promoting vaccines through primary care professionals.     

COVID-19 vaccination intention and activation among health care system employees: A mixed methods study

BackgroundAchieving high COVID-19 vaccination rates among employees is necessary to prevent outbreaks in health care settings. The goal of the study was to produce actionable and timely evidence about factors underlying the intention and decisions to obtain the COVID-19 vaccine by employees.MethodsThe study was conducted from December 2020 – May 2021 with employees from a VA health care system in Southeastern US. The study used a convergent mixed methods design comprising two main activities: a cross-sectional survey conducted prior to COVID-19 vaccine distribution, and semi-structured interviews conducted 4–6 months after vaccine distribution. Data were collected about participant characteristics, vaccination intention prior to distribution, vaccination decision post-distribution, determinants of vaccination intention and decision, activating factors, sources of information and intervention needs. Data from the survey and interviews were analyzed separately and integrated narratively in the discussion.ResultsPrior to vaccine distribution, 77% of employees wanted to be vaccinated. Post vaccine distribution, we identified 5 distinct decision-making groups: 1) vaccine believers who actively sought vaccination and included those sometimes described as “immunization advocates”, 2) go along to get along (GATGA) individuals who got vaccinated but did not actively seek it, 3) cautious acceptors who got the COVID-19 vaccine after some delay, 4) fence sitters who remained uncertain about getting vaccinated, and 5) vaccine refusers who actively rejected the COVID-19 vaccine. Participants identifying with Black or multiple races were more likely to express hesitancy in their vaccination intention.ConclusionThe findings of our study highlight distinct decision-making profiles associated with COVID-19 vaccination among employees of a VA health care system, and provide tailored recommendations to reduce vaccine hesitancy in this population.     

COVID-19 vaccine express strategy in Malawi: An effort to reach the un-reach

ObjectivesTo establish the impact of “Covid-19 Vaccination express” (CVE) on vaccine uptake in Malawi.DesignRetrospective cross-sectional study to compare the daily vaccine administration rate in CVE and routine covid vaccination (RCV). RCV data was collected from March 2021 to October 2021. The data regarding CVE was collected from 5 November 2021 to 31 December 2021. Data was collected regarding (1) the total number and type of vaccine doses administered and (2) Demographic details like age, gender, occupation, presence of comorbidities, the first dose, or the second dose of the people who received a vaccine.ResultsFrom March-December 2021, a total of 1,866,623 COVID-19 vaccine doses were administered, out of which 1,290,145 doses were administered at a mean daily vaccination rate of 1854 (95 % CI: 1292–2415) doses as a part of RCV, and 576,478 doses were administered at a mean daily vaccination rate of 3312 (95 % CI: 2377–4248) doses as a part of CVE.Comparing the mean daily doses (Astra Zeneca, AZ doses 1 & 2) administered in the CVE and RCV showed that the mean daily doses of AZ vaccine administered were significantly higher in the CVE (p < 0.05).ConclusionCVE successfully increased the uptake of the Covid-19 vaccine.     

Estimating the number of US children susceptible to measles resulting from COVID-19-related vaccination coverage declines

Measles elimination hinges on vaccination coverage remaining above 95% to retain sufficient community protection. Recent declines in routine measles vaccinations due to the COVID-19 pandemic coupled with prior models indicating the country was close to the 92% herd immunity benchmark are a cause for concern. We evaluated population-level measles susceptibility in the US, including sensitivity analyses accounting for pandemic-related impacts on immunization. We estimated the number of children aged 0–18 currently susceptible to measles and modeled susceptibility proportions in decreased vaccination scenarios. Participants were respondents to the NIS-Teen survey between 2008 and 2017 that also had provider-verified vaccination documentation. The exposure of interest was vaccination with a measles-containing vaccine (MCV), and the age at which they were vaccinated for all doses given. Using age at vaccination, we estimated age-based probabilities of vaccination and modeled population levels of MCV immunization and immunity vs. susceptibility. Currently, 9,145,026 children (13.1%) are estimated to be susceptible to measles. With pandemic level vaccination rates, 15,165,221 children (21.7%) will be susceptible to measles if no attempt at catch-up is made, or 9,454,436 children (13.5%) if catch-up vaccinations mitigate the decline by 2–3%. Models based on increased vaccine hesitancy also show increased susceptibility at national levels, with a 10% increase in hesitancy nationally resulting in 14,925,481 children (21.37%) susceptible to measles, irrespective of pandemic vaccination levels. Current levels of measles immunity remain below herd immunity thresholds. If pandemic-era reductions in childhood immunization are not rectified, population-level immunity to measles is likely to decline further.     

Development and characterization of a novel conjugated methamphetamine vaccine

BackgroundMethamphetamine (METH) addiction is a major public health concern globally with limited management options. The development of a METH vaccine through hapten design has received significant attention as a promising platform for the potential treatment of METH addiction and overdose, however there is yet to be a successful candidate in human trials.Research design and methods: In this study, we developed a novel conjugated METH vaccine using oxidized mannan (a polymannose) as an immunogenic carrier. A METH hapten was synthesized by using amphetamine and conjugated to mannan with a (Lysine-Glycine-Lysine-Glycine-lysine-Glycine-Lysine-Glycine-Lysine-Glycine) (KG)₅ peptide linker.ResultsThe reaction between amphetamine and (KG)₅, oxidation of mannan, and conjugation of amphetamine-(KG)₅ with oxidized mannan were confirmed by color tests, Fourier-transform infrared spectroscopy, gas and liquid chromatography mass spectrometry, thin-layer chromatography, and ultraviolet spectrophotometer. Additionally, the ability of the vaccine to generate antibodies was confirmed in C57BL/6 mice.ConclusionsThe successful development and characterization of the METH-mannan conjugate vaccine, provides a potential therapeutic intervention to curb METH substance use disorders. Each step of vaccine development was characterized to aid in future research on these vaccines, and the immunogenicity shown in the animal models supports future evaluation of the approach. Future studies of the conjugated METH vaccine should evaluate the efficacy in animal models of acute and chronic METH to pave the way for human studies.     

Impact of rotavirus vaccination on diarrheal hospitalizations in children younger than 5 years of age in a rural southern Mozambique

BackgroundRotavirus vaccine (Rotarix®) was introduced in Mozambique through its Expanded Program of Immunization in September 2015. We assessed the impact of rotavirus vaccination on childhood gastroenteritis-associated hospitalizations post-vaccine introduction in a high HIV prevalence rural setting of southern Mozambique.MethodsWe reviewed and compared the trend of hospitalizations (prevalence) and incidence rates of acute gastroenteritis (AGE), and rotavirus associated-diarrhea (laboratory confirmed rotavirus) in pre- (January 2008–August 2015) and post-rotavirus vaccine introduction periods (September 2015–December 2020), among children <5 years of age admitted to Manhiça District Hospital.ResultsFrom January 2008 to December 2020, rotavirus vaccination was found to contribute to the decline of the prevalence of AGE from 19% (95% CI: 18.14–20.44) prior to the vaccine introduction to 10% (95% CI: 8.89–11.48) in the post-introduction period, preventing 40% (95 % IE: 38–42) and 84% (95 % IE: 80–87) of the expected AGE and laboratory confirmed rotavirus cases, respectively, among infants. Similarly, the overall incidence of rotavirus was 11.8-fold lower in the post-vaccine introduction period (0.4/1000 child-years-at-risk [CYAR]; 95% CI: 0.3–0.6) compared with the pre-vaccination period (4.7/1000 CYAR; 95% CI: 4.2–5.1) with the highest reduction being observed among infants (16.8-fold lower from the 15.1/1000 CYAR in the pre-vaccine to 0.9/1000 CYAR in the post-vaccine eras).ConclusionsWe documented a significant reduction in all-cause diarrhea hospitalizations and rotavirus positivity after vaccine introduction demonstrating the beneficial impact of rotavirus vaccination in a highly vulnerable population.     

Individual-level factors associated with COVID-19 vaccine acceptance among U.S. patients with cancer

IntroductionVaccine hesitancy in the wake of the COVID-19 pandemic is a major public health concern in the US. Cancer patients are especially vulnerable to adverse COVID-19 outcomes and require targeted prevention efforts against COVID-19.MethodsWe used longitudinal survey data from patients seen at Moffitt Cancer Center to identify attitudes, beliefs, and sociodemographic factors associated with COVID-19 vaccination acceptance among cancer patients. Patients with confirmed invasive cancer diagnosis through Cancer Registry data were asked about vaccine acceptance through the question “Now that a COVID-19 vaccine is available, are you likely to get it?” and dichotomized into high accepters (already received it, would get it when available) and low accepters (waiting for a doctor to recommend it, waiting until more people received it, not likely to get it).ResultsMost patients (86.8% of 5,814) were high accepters of the COVID-19 vaccine. High accepters had more confidence in the effectiveness and safety of the vaccine than low accepters. Multivariable logistic regression showed older individuals (70–89 vs.18–49: OR:2.57, 95% CI:1.33–4.86), those with greater perceived severity of COVID-19 infection (very serious vs. not at all serious: OR:2.55, 95% CI:1.76–3.70), practicing more risk mitigation behaviors (per one standard deviation OR:1.75, 95% CI:1.57–1.95), and history of receiving the flu shot versus not (OR:6.56, 95% CI:5.25–8.20) had higher odds of vaccine acceptance. Individuals living with more than one other person (vs. alone: OR: 0.53, 95% CI: 0.35, 0.79) and those who were more socioeconomically disadvantaged (per 10 percentile points: OR: 0.89, 95 %CI: 0.85, 0.93) had lower odds of reporting vaccine acceptance.ConclusionMost patients with cancer have or would receive the COVID-19 vaccine. Those who are less likely to accept the vaccine have more concerns regarding effectiveness and side effects, are younger, more socioeconomically disadvantaged, and have lower perceptions of COVID-19 severity.     

Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine

Clostridium perfringens is a normal bacterial flora of the small and large intestines of humans and other animals. The current study investigates the potential use of a noncytotoxic C. perfringens as an oral vaccine vehicle for expression and intestinal delivery of a large amount of SIV antigens. Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation. Following oral administration of this recombinant C. perfringens vaccine vector to mice, large amounts of intact p27 protein were detected in the terminal ileum where the majority of Peyer's Patches (PPs) are located. Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen. In addition, uptake of C. perfringens was able to induce maturation of mouse DCs. These results support the potential use of C. perfringens as an oral SIV/HIV vaccine vector.     

Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18

Sensitive high-throughput neutralization assays, based upon pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter gene, were developed and validated for human papillomavirus (HPV)16, HPV18, and bovine papillomavirus 1 (BPV1). SEAP pseudoviruses were produced by transient transfection of codon-modified papillomavirus structural genes into an SV40 T antigen expressing line derived from 293 cells, yielding sufficient pseudovirus from one flask for thousands of titrations. In a 96-well plate format, in this initial characterization, the assay was reproducible and appears to be as sensitive as, but more specific than, a standard papillomavirus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). The neutralization assay detected type-specific HPV16 or HPV18 neutralizing antibodies (titers of 160-10240) in sera of the majority of a group of women infected with the corresponding HPV type, but not in virgin women. Sera from HPV16 VLP vaccinees had high anti-HPV16 neutralizing titers (mean: 45000; range: 5120-163840), but no anti-HPV18 neutralizing activity. The SEAP pseudovirus-based neutralization assay should be a practical method for quantifying potentially protective antibody responses in HPV natural history and prophylactic vaccine studies.