COVID-19 vaccine – Long term immune decline and breakthrough infections

BackgroundSince the introduction of BNT162b2 mRNA COVID-19 vaccine by Pfizer in late 2020, efficacy and immunogenicity waning of COVID-19 vaccines was reported, and decision making regarding a booster remains a top priority worldwide, a decision that should be made based on breakthrough infection rate and antibody titer decline overtime.MethodsWe conducted a 5-month longitudinal prospective study involving vaccinated healthcare personnel, who were tested monthly for antibody titer, and sampled biweekly and on clinical indication for SARS-COV-2 polymerase chain reaction (PCR), to determine antibody decline and breakthrough infection.Results100 participants were recruited to the study. Antibody titer reached the climate after one month of the second dose of the vaccine, and declined rapidly thereafter: the median antibody levels were 895; 22,266; 9,682; 2,554 and 1,401 AU/ml in the day of the second dose, and in one month interval thereafter, respectively. In other words, four months after vaccination, the mean antibody level was 6% of the peak levels. During the study period, 4 breakthrough infections were diagnosed, 2 of which were asymptomatic, and the remaining two were mild cases; sharp elevation of antibody titer was seen after infection.ConclusionAntibody titer drops rapidly one month after the second dose of the vaccine. All infections within the study period were mild or asymptomatic, after which titer elevations were seen.     

Evaluation of a Campylobacter jejuni N-glycan-ExoA glycoconjugate vaccine to reduce C. jejuni colonisation in chickens

Campylobacter jejuni is the leading bacterial cause of human gastroenteritis worldwide and handling or consumption of contaminated poultry meat is the key source of infection. Glycoconjugate vaccines containing the C. jejuni N-glycan have been reported to be partially protective in chickens. However, our previous studies with subunit vaccines comprising the C. jejuni FlpA or SodB proteins with up to two or three C. jejuni N-glycans, respectively, failed to elicit significant protection. In this study, protein glycan coupling technology was used to add up to ten C. jejuni N-glycans onto a detoxified form of Pseudomonas aeruginosa exotoxin A (ExoA). The glycoprotein, G-ExoA, was evaluated for efficacy against intestinal colonisation of White Leghorn chickens by C. jejuni strains M1 and 11168H relative to unglycosylated ExoA. Chickens were challenged with the minimum dose required for reliable colonisation, which was 10² colony-forming units (CFU) for strain M1 and and 10⁴ CFU for strain 11168H. Vaccine-specific serum IgY was detected in chickens vaccinated with both ExoA and G-ExoA. However, no reduction in caecal colonisation by C. jejuni was observed. While the glycan dose achieved with G-ExoA was higher than FlpA- or SodB-based glycoconjugates that were previously evaluated, it was lower than that of glycoconjugates where protection against C. jejuni has been reported, indicating that protection may be highly sensitive to the amount of glycan presented and/or study-specific variables.     

Priming with social benefit information of vaccination to increase acceptance of COVID-19 vaccines

Vaccine hesitancy can be heightened due to increasing negative reports about vaccines. Emphasizing the social benefits of vaccination may shift individual attention from individual to social benefit of vaccination and hence promote prosocial vaccination. In six rounds of a population-based survey conducted over one major community epidemic of coronavirus disease 2019 (COVID-19) in Hong Kong from June to November 2020, we manipulated the question asking about acceptance of a COVID-19 vaccine with or without emphasizing the social benefit of vaccination against COVID-19 (prosocial priming) and monitored the changes of vaccine confidence by news media sentiment on vaccines. Population-weighted percentages of accepting COVID-19 vaccines by priming condition and vaccine confidence were compared across survey rounds. Logit regression models assessed the main effect of prosocial priming and the modification effects of vaccine confidence and perceived personal risk from COVID-19 on acceptance of COVID-19 vaccines. We found that prosocial priming significantly increased acceptance of COVID-19 vaccines across all survey rounds except for Round 3 when incidence of COVID-19 reached a peak. Vaccine confidence significantly declined in Round 6 when news media sentiment on vaccines became predominantly negative. The effect of prosocial priming on promoting vaccine acceptance was significantly greater in participants with low vaccine confidence and those perceiving the severity of COVID-19 to be mild/very mild. Our study suggests that packaging vaccination against COVID-19 as a prosocial behaviour can help overcome low vaccine confidence and promote prosocial vaccination particularly when disease incidence temporarily declines and the public perceive low severity of COVID-19.     

The cost-effectiveness of starting 23-valent pneumococcal polysaccharide vaccine and influenza vaccination at 50 vs. 65 years: A comparative modelling study

ObjectivesPneumococcal infection is a leading cause of morbidity and mortality. We aimed to evaluate the cost-effectiveness of 23-valent polysaccharide vaccine (PPV23) together with influenza vaccination or pneumococcal vaccination alone in adults starting from 50 years vs. 65 years in Hong Kong.MethodsA hypothetical population of 100,000 older adults was included in a Markov model with age ranging from 50 to 85 years to calculate the cost and quality-adjusted life-years (QALYs) gained for vaccination strategies, including: (1) annual influenza vaccine and PPV23 at 50 and 65 years; (2) annual influenza vaccine and PPV23 at 65 years (similar with the current vaccination programme); (3) PPV23 at 50 and 65 years; (4) PPV23 at 65 years; and (5) no vaccination. We evaluated the incremental cost-effectiveness ratio (ICER) and used Monte Carlo simulation for probabilistic sensitivity analysis. The cost-effectiveness threshold was extracted from previous literature.ResultsIn comparison with no vaccination, all strategies were cost-effective with ICERs less than the threshold (US$24,302 per QALY gained). When compared with no vaccination, strategies 1–4 saved US$ 49.5, US$ 94.9, US$ 584.3, and US$ 1114.2 to gain one QALY respectively. In comparison with strategy 2, strategy 1 spent US$ 195.3 to gain one QALY, whilst strategies 3 and 4 showed less effectiveness with increased costs.ConclusionsAll vaccination strategies were cost-effective, among which the strategy of PPV23 at 50/65 years with annual influenza vaccine was cost-effective even in comparison with current vaccination programme. These findings could help inform the design and implementation of vaccination strategies.     

Aggregating human judgment probabilistic predictions of the safety,efficacy, and timing of a COVID-19 vaccine

Safe, efficacious vaccines were developed to reduce the transmission of SARS-CoV-2 during the COVID-19 pandemic. But in the middle of 2020, vaccine effectiveness, safety, and the timeline for when a vaccine would be approved and distributed to the public was uncertain. To support public health decision making, we solicited trained forecasters and experts in vaccinology and infectious disease to provide monthly probabilistic predictions from July to September of 2020 of the efficacy, safety, timing, and delivery of a COVID-19 vaccine. We found, that despite sparse historical data, a linear pool—a combination of human judgment probabilistic predictions—can quantify the uncertainty in clinical significance and timing of a potential vaccine. The linear pool underestimated how fast a therapy would show a survival benefit and the high efficacy of approved COVID-19 vaccines. However, the linear pool did make an accurate prediction for when a vaccine would be approved by the FDA. Compared to individual forecasters, the linear pool was consistently above the median of the most accurate forecasts. A linear pool is a fast and versatile method to build probabilistic predictions of a developing vaccine that is robust to poor individual predictions. Though experts and trained forecasters did underestimate the speed of development and the high efficacy of a SARS-CoV-2 vaccine, linear pool predictions can improve situational awareness for public health officials and for the public make clearer the risks, rewards, and timing of a vaccine.     

A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report

IntroductionThe mRNA vaccine, mRNA-1273/TAK-919, encodes the prefusion-stabilised spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report interim results of the first study evaluating safety and immunogenicity of mRNA-1273 in healthy Japanese participants.MethodsThis phase 1/2, randomised, observer-blind, placebo-controlled trial, conducted in Japan (two sites), enrolled healthy adults aged ≥ 20 years with no prior exposure to investigational coronavirus vaccines/treatments, and no known history/risk of SARS-CoV-2 infection. Participants were stratified by age (< 65/≥ 65 years) and randomised to receive two doses of 100 μg mRNA-1273 or placebo administered as intramuscular injections 28 days apart. Primary outcomes were safety and immunogenicity assessed by anti-SARS-CoV-2-spike protein-binding antibody level (bAb). A secondary outcome was SARS-CoV-2 neutralising antibody (nAb) response.ResultsParticipants were enrolled between 21 January and 3 February 2021, and 200 were randomised: mRNA-1273, n = 150 (< 65 years, n = 100; ≥ 65 years, n = 50); placebo, n = 50 (< 65 years, n = 40; ≥ 65 years, n = 10). Solicited adverse events (AEs) through 7 days after each vaccination occurred in 144/150 (96%) and 19/50 (38%) participants in the mRNA-1273 and placebo arms, respectively. In the mRNA-1273 arm, injection-site pain, myalgia and fatigue were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with mRNA-1273 (n = 147) with a bAb geometric mean fold rise (95% confidence interval [CI]) from baseline of 1009 (865, 1177) and a nAb of 21.7 (19.8, 23.8) at day 57. Seroconversion rates (95% CI) for bAb and nAb were both 100% (97.5, 100) at day 57. No such response occurred with placebo (n = 49).ConclusionTwo doses of 100 μg mRNA-1273 given 28 days apart demonstrated an acceptable safety profile and induced significant anti-SARS-CoV-2 immune responses in a Japanese population aged ≥ 20 years. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov: NCT04677660.     

Looking ahead: Caregivers’ COVID-19 vaccination intention for children 5 years old and younger using the health belief model

COVID-19 vaccine hesitancy is a significant public health issue. While vaccines are not yet available for children, clinical trials are underway, and children will likely be an important factor in the U.S. reaching herd immunity. However, little research has been conducted to examine parents’ intention to vaccinate their young children for COVID-19.MethodAn online survey with a national U.S. sample of 682 primary caregivers of children under age six assessed variables associated with intention to accept the COVID-19 vaccine for their children from November 13, 2020, to December 8, 2020.ResultsCaregivers whose child received a recent influenza vaccine, as well as those with previous experience COVID-19, were more likely to express COVID-19 vaccination intention for their young child. Identifying as female was associated with lower COVID-19 vaccination intention, while identifying as Hispanic or Latino was associated with higher intention. Health Belief Model variables of perceived severity of COVID-19 for their child, as well as vaccine confidence, were positive predictors of COVID-19 vaccine intention and mediated the relationship between prior behavior, demographic variables, and intention.ConclusionsThe findings highlight the importance of early, proactive COVID-19 vaccination education efforts directed at caregivers, including those with young children. Vaccines for young children will likely become a necessary part of ending the pandemic’s impact in school settings. Operationally, COVID-19 vaccination may also become a part of childhood vaccination schedules. Understanding the beliefs and intentions of caregivers of young children before vaccinations are recommended for children will enable public health officials and medical practitioners to prepare in advance.     

How frequent are acute reactions to COVID-19 vaccination and who is at risk?

IntroductionOur objective was to describe and compare self-reported side effects of COVID-19 vaccines in the USA.MethodsA web-based registry enrolled volunteers who received a COVID-19 vaccine between March 19–July 15, 2021. We collected self-reported short-term side effects, medical consultation, hospitalization, and quality of life impact following completed vaccination regimens (Pfizer, Moderna, J&J).ResultsWe recruited 6,966 volunteers who completed their full course of vaccination (median age 48 years, IQR 35.0–62.0; 83.6% female): Pfizer 3,486; Moderna 2,857; J&J 623. Few (3.1%) sought medical care for post-vaccination side effects. Hospitalization (n = 17; 0.3%) and severe allergic reactions (n = 39; 0.6%) also were rare. Those with autoimmune disease or lung disease were approximately twice as likely to seek medical care (adjusted odds ratio (aOR) 2.01, 95% CI:1.39; 2.92 and aOR 1.70, 95% CI: 1.12; .58 respectively). 92.4% of participants reported ≥ 1 side effect (median 3), with injection site reactions (78.9%), fatigue (70.3%), headache (49.0%) reported most frequently. More side effects were reported after the second dose of two-dose vaccines (medians: 1 vs. 2 for Pfizer and 1 vs. 3 for Moderna for first and second doses respectively) versus 3 for J&J's single-dose vaccine. For the employed, the median number of workdays missed was one. Diabetics and those vaccinated against influenza were substantially less likely to report 3 or more symptoms (aOR 0.68, 95% CI: 0.56;0.82] and aOR 0.82, 95% CI: 0.73;0.93, respectively).DiscussionThe total side effect burden was, not unexpectedly, greater with two-dose regimens but all three vaccines appear relatively safe. Very few subjects reported side effects serious enough to warrant medical care or reported post-vaccination hospitalization. While these findings do not address possible long-term effects, they do inform on their short-term safety and tolerability and will hopefully provide some reassurance and positively inform the benefit-risk and pharmacoeconomic assessment for all three vaccines.See Clinicaltrials.gov NCT04368065.     

Effective improvements to the live-attenuated Newcastle disease virus vaccine by polyethylenimine-based biomimetic silicification

Live and killed vaccines impart a significant role in preventing of Newcastle disease (ND) in China. Vaccine efficacy could be ameliorated by improving vaccine-induced cellular immunity and antibody persistency. Previous studies substantiated the potency of silicon dioxide (SiO₂) in the control-release of drugs and as a vaccine adjuvant, and polyethylenimine (PEI) merits as a mucosal adjuvanticity with electro-positivity. The present study employed SiO₂ and PEI to prepare biomimetic silicon mineralized nanoparticle G7M@SiO₂-PEI and microparticle (SiO₂ + PEI)@G7M vaccines of G7M, a candidate for live attenuated vaccine of genotype VII Newcastle disease virus (NDV). The zeta potential experiment confirmed the significant increase in the average zeta potential of the nanoparticle G7M@SiO₂-PEI and microparticle (SiO₂ + PEI)@G7M relative to G7M before mineralization. The results of RT-qPCR revealed more than 99% mineralization efficiency of the G7M@SiO₂-PEI and (SiO₂ + PEI)@G7M. The morphology detected by transmission electron microscopy reported that the diameters of G7M@SiO₂-PEI were similar to those of G7M, while for (SiO₂ + PEI)@G7M, it was about five times larger than that of G7M. Silicon was detected on the surface of both mineralization particles, except for G7M, as observed from the elemental distribution detected by elemental mapping and energy dispersive X-ray spectrogram. Indirect immunofluorescence assays validated that mineralization virus have replicated ability in BHK-21F cells. In vivo experiments revealed higher than 5.50 log₂ of antibody in nanoparticles G7M@SiO₂-PEI group until 10-week post-vaccination, and significant proliferation of antigen-specific CD3⁺CD4⁺ in nanoparticles G7M@SiO₂-PEI immunized group corroborated improved cellular immune responses. Vaccines provided full protection to the immunized chickens, whereas all the chickens receiving mock immunizations succumbed to the disease. Overall, our study concluded the efficacy of biomimetic mineralization of live attenuated vaccine in nanoparticles to improve humoral and cellular immune responses.