Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.     

Antibody dependent disease enhancement (ADE) after COVID-19 vaccination and beta glucans as a safer strategy in management

A potential risk associated with vaccines for COVID-19 is antibody-dependent disease enhancement (ADE) in which vaccine induced antibody mediated immune responses may lead to enhanced SARS CoV- 2 acquisition or increased disease severity. Though ADE has not been clinically demonstrated with any of the COVID-19 vaccines so far, when neutralizing antibodies are suboptimal, the severity of COVID-19 has been reported to be greater. ADE is presumed to occur via abnormal macrophages induced by the vaccine based immune response by antibody-mediated virus uptake into Fc gamma receptor IIa (FcγRIIa) or by the formation of Fc-mediated excessive antibody effector functions. Beta-glucans which are naturally occurring polysaccharides known for unique immunomodulation by capability to interact with macrophages, eliciting a specific beneficial immune-response and enhancing all arms of the immune system, importantly without over-activation are suggested as safer nutritional supplement-based vaccine adjuvants for COVID-19.     

Assessing the long-stand antibody response induced by COVID-19 vaccines: A study in an educational cohort in San Luis,Argentina

BackgroundAlthough there has developed an increased interest in the vaccines BNT1622b2 (Pfizer/BioNTech), mRNA-1273 (Moderna/NIAID), and ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford), there are still few reports describing the immune response induced by different vaccine platforms in real-world settings of low-income countries. Here, we proposed to analyse the humoral immune response elicited by the primary vaccines used in Argentina from July-December 2021.MethodsAnti-SARS-CoV-2-Spike-RBD IgG and neutralising antibodies were assayed by ELISA in a total of 871 serum samples obtained from 376 volunteers from an educational staff. The individuals were vaccinated with BBIBP-CorV (Sinopharm), ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford, AZ), Gam-COVID-Vac (Sputnik V, SpV) or combined vaccines (mostly SpV and mRNA-1273, Moderna). The antibody response was analysed several days after the initial vaccination (20, 40, 120 and 180 days).ResultsAfter receiving at least one dose of the COVID-19 vaccine, we detected 93.34% of seroprevalence. Previously SARS-CoV-2 infected showed higher antibody concentrations compared with naïve vaccinees. Six months after the initial vaccination, combined vaccination induced higher anti-SARS-CoV-2 antibody levels than the other vaccines in naïve volunteers. However, we did not find differences in the neutralising responses after any vaccine from naïve vaccines or between the naïve and previously infected volunteers on day 120 after vaccination.ConclusionsOur long-term analysis of volunteers from the educational system provides data in a real-world context, showing the benefits of a boost dose still in previously infected volunteers, and suggesting the advantages of a heterologous prime-boost schedule.     

Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters

COVID-19 presents an ongoing global health crisis. Protein-based COVID-19 vaccines that are well-tolerated, safe, highly-protective and convenient to manufacture remain of major interest. We therefore sought to compare the immunogenicity and protective efficacy of a number of recombinant SARS-CoV-2 spike protein candidates expressed in insect cells. By comparison to a full length (FL) spike protein detergent-extracted nanoparticle antigen, the soluble secreted spike protein extracellular domain (ECD) generated higher protein yields per liter of culture and when formulated with either Alum-CpG55.2 or Advax-CpG55.2 combination adjuvants elicited robust antigen-specific humoral and cellular immunity in mice. In hamsters, the spike ECD when formulated with either adjuvant induced high serum neutralizing antibody titers even after a single dose. When challenged with the homologous SARS-CoV-2 virus, hamsters immunized with the adjuvanted spike ECD exhibited reduced viral load in day 1–3 oropharyngeal swabs and day 3 nasal turbinate tissue and had no recoverable infectious virus in day 3 lung tissue. The reduction in lung viral load correlated with less weight loss and lower lung pathology scores. The formulations of spike ECD with Alum-CpG55.2 or Advax-CpG55.2 were protective even after just a single dose, although the 2-dose regimen performed better overall and required only half the total amount of antigen. Pre-challenge serum neutralizing antibody levels showed a strong correlation with lung protection, with a weaker correlation seen with nasal or oropharyngeal protection. This suggests that serum neutralizing antibody levels may correlate more closely with systemic, rather than mucosal, protection. The spike protein ECD with Advax-CpG55.2 formulation (Covax-19® vaccine) was selected for human clinical development.     

NIH funding for vaccine readiness before the COVID-19 pandemic

Rapid development of vaccines for COVID-19 has relied on the application of existing vaccine technologies. This work examines the maturity of ten technologies employed in candidate vaccines (as of July 2020) and NIH funding for published research on these technologies from 2000–2019. These technologies vary from established platforms, which have been used successfully in approved products, to emerging technologies with no prior clinical validation. A robust body of published research on vaccine technologies was supported by 16,358 fiscal years of NIH funding totaling $17.2 billion from 2000–2019. During this period, NIH funding for published vaccine research against specific pandemic threats such as coronavirus, Zika, Ebola, and dengue was not sustained. NIH funding contributed substantially to the advance of technologies available for rapid development of COVID-19 vaccines, suggesting the importance of sustained public sector funding for foundational technologies in the rapid response to emerging public health threats.     

Hypertension is associated with antibody response and breakthrough infection in health care workers following vaccination with inactivated SARS-CoV-2

Several types of vaccines have been developed to prevent the coronavirus disease 2019 (COVID-19). It is important to understand whether demographic and clinical variables affect the effectiveness of various types of vaccines. This study analysed the association between demographic/clinical factors, antibody response and vaccine effectiveness in healthcare workers vaccinated with inactivated virus.We enrolled 101 healthcare workers who received two doses of inactivated viral vaccine (CoronaVac). Blood samples were analysed at 1, 3, and 5 months after the second dose of vaccination. Data regarding demographic characteristics, medical histories, and clinical parameters were collected by interview and medical examination. In a separate retrospective study, we analysed the incidence of vaccine breakthrough infection on 2714 healthcare workers who received two doses of inactivated viral vaccine. Medical histories and demographic data were collected using a structured self-reported questionnaire.We found that antibody titres markedly increased at 1 month after vaccination but gradually decreased at 3–5 months post-vaccination. We observed a significant association between age (≥40 years) and antibody level, whereas sex and body mass index (BMI) exhibited no effect on antibody titres. Amongst clinical variables analysed, high blood pressure and history of hypertension were significantly correlated with lower antibody titres. Consistently, we found a significant association in the retrospective study between hypertension and the incidence of breakthrough infection.In conclusion, our results showed that hypertension is associated with lower antibody titres and breakthrough infection following COVID-19 vaccination. Thus, blood pressure control might be important to improve the efficacy of inactivated virus vaccine.     

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.     

An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits highly potent immunity

We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein and several adjuvants in an effort to identify a highly potent Coronavirus disease 2019 (COVID-19) vaccine candidate. eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced high antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, named VBI-2902a, protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a highly potent vaccine against COVID-19.     

Deletion of major porins from meningococcal outer membrane vesicle vaccines enhances reactivity against heterologous serogroup B Neisseria meningitidis strains

Detergent-extracted detoxified outer membrane vesicle (dOMV) vaccines are effective at preventing invasive serogroup B meningococcal (MenB) disease caused by the homologous Neisseria meningitidis strain from which they are produced, but offer limited protection from heterologous strains. Differences in vaccine efficacy are partially due to strain-specific variations in the antigenic sequence types and expression levels of outer membrane proteins (OMPs), including the immunodominant OMP PorA. In this study, dOMV vaccines deficient in major OMPs, including PorA, PorB, and RmpM were isolated and used to immunize rabbits and mice. Serum samples were obtained from each animal and tested for antibody responses against five MenB strains. Immunization with wild type dOMVs elicited antibodies to major antigens including PorA, PorB, RmpM, and lipooligosaccharide (LOS), and demonstrated limited bactericidal activity against heterologous strains. In contrast, OMP-deficient dOMV vaccines elicited broadly cross-reactive bactericidal antibodies, with PorA/PorB-dual deficient dOMVs inducing antibodies exhibiting the greatest cross-reactivity. Enhanced killing of heterologous strains correlated with binding to unique protein bands in immunoblots, suggestive of improved immunogenicity of antigens under-represented in the wild type vaccine.     

RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice

The COVID-19 pandemic has spurred an unprecedented movement to develop safe and effective vaccines against the SARS-CoV-2 virus to immunize the global population. The first set of vaccine candidates that received emergency use authorization targeted the spike (S) glycoprotein of the SARS-CoV-2 virus that enables virus entry into cells via the receptor binding domain (RBD). Recently, multiple variants of SARS-CoV-2 have emerged with mutations in S protein and the ability to evade neutralizing antibodies in vaccinated individuals. We have developed a dual RBD and nucleocapsid (N) subunit protein vaccine candidate named RelCoVax® through heterologous expression in mammalian cells (RBD) and E. coli (N). The RelCoVax® formulation containing a combination of aluminum hydroxide (alum) and a synthetic CpG oligonucleotide as adjuvants elicited high antibody titers against RBD and N proteins in mice after a prime and boost dose regimen administered 2 weeks apart. The vaccine also stimulated cellular immune responses with a potential Th1 bias as evidenced by increased IFN-γ release by splenocytes from immunized mice upon antigen exposure particularly N protein. Finally, the serum of mice immunized with RelCoVax® demonstrated the ability to neutralize two different SARS-CoV-2 viral strains in vitro including the Delta strain that has become dominant in many regions of the world and can evade vaccine induced neutralizing antibodies. These results warrant further evaluation of RelCoVax® through advanced studies and contribute towards enhancing our understanding of multicomponent subunit vaccine candidates against SARS-CoV-2.     

Consensus summary report for CEPI/BC March 12–13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of “disease enhancement” has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.     

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination.A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44–0.88 log₁₀ higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55–1.77 for IgG, 1.00–1.78 for live virus nAb and 1.79–2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.     

An Advax-CpG55.2™ adjuvanted recombinant spike protein vaccine protects cynomolgus macaques from a homologous SARS-CoV-2 virus challenge

Traditional protein-based vaccine approaches to COVID-19 were overshadowed by the new mRNA and adenoviral vector vaccine approaches which were first to receive marketing authorization. The current study tested for the first time in repurposed aged (median 15.4 years) cynomolgus macaques, a novel Advax-CpG55.2™ adjuvanted recombinant extracellular domain spike protein trimer antigen for immunogenicity, protection and safety. Nine animals received two intramuscular injections 10 days apart of recombinant spike protein (25 μg) with Advax-CpG55.2™ (10 mg/200 μg) and 5 controls received saline injections. Serum antibody levels were followed for 3 months and then the animals were challenged with SARS-CoV-2 virus. Clinical signs, local reactions, body weight, food consumption and antibody levels were monitored till termination on either day 3 or 7 post-infection. Two weeks after the second dose, 8/9 immunized macaques had high serum spike and receptor binding domain binding antibodies that were able to cross-neutralize Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and, to a lesser extent, Omicron variants (B.1.1.529 ). Antibody levels decayed over the subsequent 3 months, and minimal neutralizing antibody was detectable immediately prior to the challenge which used a vaccine-homologous Wuhan-like ancestral virus. Of the nine vaccinated animals, only one 18-year-old female sacrificed at d3 had low levels of lung virus, versus 100 % of the control animals. Four of 5 (80 %) control animals had positive lung staining for SARS-CoV-2 virus versus just 1 of 9 (11 %) in the immunized group. The immunized animals exhibited better maintenance of appetite post-challenge. Neutralizing antibody levels rebounded rapidly in immunized animals, post-challenge. This data supports the benefits of Advax-CpG adjuvanted recombinant spike protein vaccine in protecting against a homologous SARS-CoV-2 infection.     

COVID-19 and gut dysbiosis,understanding the role of probiotic supplements in reversing gut dysbiosis and immunity

In December 2019, an outbreak of novel beta-coronavirus started in Wuhan, China, spread globally as coronavirus disease 2019 (COVID-19) pandemic and is still underway. The causative agent for COVID-19 identified as a novel strain of beta coronavirus named nSARS-CoV-2. The nSARS-CoV-2 primarily targets the respiratory tract and results in severe acute respiratory distress (ARDS), leading to the collapse of the respiratory tract. The virus internalizes primarily via ACEII receptor, and many tissues reported a significant level of expression of ACEII receptor including lungs, hearts, kidneys, and gastrointestinal tract. The clinical manifestations of COVID-19 are diverse, but growing evidence suggests that gut dysbiosis is one of them and poses a threat to native immunity. The human microbial ecology plays a vital role in human physiology, including building immunity. The gastrointestinal tract (GIT) habitats trillions of beneficial microbes’ precisely bacterial species synchronize with human physiology and remain symbiotic. On the contrary, harmful microbiota seeks an opportunity to break the equilibrium failure of balance between beneficial and detrimental human gut microbiota results in impaired physiology and immunity. The grown research evidence demonstrated that infection caused by the nSARS-CoV-2 result in moderate to severe diarrheal outcomes. The diarrheal conditions in COVID-19 patients are due to alteration of gut microbial ecology. The management of COVID-19 requires specialized therapeutics along with a series of nutraceuticals. Probiotics remain vital nutrient supplements in COVID-19 management, offer relief in diarrhea and improve/restore immunity. This study uses available data/findings to emphasize an association between COVID-19 and gut dysbiosis. The study also provides a scientific basis of impaired immunity during gut dysbiosis in COVID-19 and how probiotics help restore and improve impaired immunity and diarrhea.     

Effect of adjuvanting RBD-dimer-based subunit COVID-19 vaccines with Sepivac SWE™

Protein subunit vaccines have been widely used to combat infectious diseases, including the current COVID-19 pandemic. Adjuvants play the key role in shaping the quality and magnitude of the immune response to protein and inactivated vaccines. We previously developed a protein subunit COVID-19 vaccine, termed ZF2001, based on an aluminium hydroxide-adjuvanted tandem-repeat dimeric receptor-binding domain (RBD) of the viral spike (S) protein. Here, we described the use of a squalene-based oil-in-water adjuvant, Sepivac SWE™ (abbreviated to SWE), to further improve the immunogenicity of this RBD-dimer-based subunit vaccines. Compared with ZF2001, SWE adjuvant enhanced the antibody and CD4⁺ T-cell responses in mice with at least 10 fold of dose sparing compared with ZF2001 adjuvanted with aluminium hydroxide. SWE-adjuvanted vaccine protected mice against SARS-CoV-2 challenge. To ensure adequate protection against the currently circulating Omicron variant, we evaluated this adjuvant in combination with Delta-Omicron chimeric RBD-dimer. SWE significantly increased antibody responses compared with aluminium hydroxide adjuvant and afforded greater neutralization breadth. These data highlight the advantage of emulsion-based adjuvants to elevate the protective immune response of protein subunit COVID-19 vaccines.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Response to mRNA COVID-19 vaccination in three XLA patients

X-linked agammaglobulinemia (XLA) is an inborn error of immunity characterized by insufficient production of immunoglobulins and lack of measurable antibody response to vaccines. The rise of novel infections limits the protective effect of immunoglobulin replacement in immunodeficient patients though. While XLA patients are not expected to mount an antibody response to COVID-19 vaccination, it has been demonstrated that XLA patients can mount a T-cell response to COVID-19 vaccines, similar to the influenza vaccine. We present three patients with XLA who received an mRNA COVID-19 vaccine. One patient demonstrated positive antibody response. Many XLA patients do not receive routine vaccinations due to ongoing immunoglobulin replacement therapy and lack of native antibody production, but in addition to T-cell response to vaccination, select XLA patients may mount a positive antibody response. Therefore, COVID-19 vaccination should be encouraged for all XLA patients.     

School immunization coverage in adolescents during the COVID-19 pandemic: A retrospective cohort study

IntroductionFew studies have assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on immunization coverage for adolescents, and little is known about how coverage has changed throughout the pandemic. We aimed to: (1) assess the change in coverage for school-based vaccines in Alberta, Canada resulting from the pandemic; (2) determine whether coverage differed by geographic health zone and school type; and (3) ascertain whether coverage has returned to pre-pandemic levels.MethodsUsing a retrospective cohort design, we used administrative health data to compare coverage for human papillomavirus (HPV) and meningococcal conjugate A, C, Y, W-135 (MenC-ACYW) vaccines between pre-pandemic (2017–2018 school year) and pandemic (2019–2020 and 2020–2021 school years) cohorts (N = 289,420). Coverage was also compared by health zone and authority type. The 2019–2020 cohort was followed over one year to assess catch-up.ResultsCompared to 2017–2018, immunization coverage for HPV was significantly lower in the 2019–2020 (absolute difference: 60.8%; 95% CI: 60.4–61.3%) and 2020–2021 cohorts (absolute difference: 59.9%; 95% CI: 59.4–60.3%). There was a smaller, significant decline in MenC-ACYW coverage comparing 2017–2018 to 2019–2020 (absolute difference: 6.1%; 95% CI: 5.6–6.5%) and 2020–2021 (absolute difference: 32.2%; 95% CI: 31.6–32.7%). Private schools had low coverage overall, while coverage fluctuated by zone. During follow-up of the 2019–2020 cohort, coverage for HPV and MenC-ACYW increased from 5.6% to 50.2%, and 80.7% to 83.0%, respectively.ConclusionThere was a substantial decrease in school-based immunization coverage during the COVID-19 pandemic, and coverage has not returned to pre-pandemic levels, suggesting further catch-up is needed.     

Intention of nurses to accept coronavirus disease 2019 vaccination and change of intention to accept seasonal influenza vaccination during the coronavirus disease 2019 pandemic: A cross-sectional survey

BackgroundMaintaining health of healthcare workers with vaccination is a major component of pandemic preparedness and acceptance of vaccinations is essential to its success. This study aimed to examine impact of the coronavirus disease 2019 (COVID-19) pandemic on change of influenza vaccination acceptance and identify factors associated with acceptance of potential COVID-19 vaccination.MethodA cross-sectional self-administered anonymous questionnaire survey was conducted among nurses in Hong Kong, China during 26 February and 31 March 2020. Their previous acceptance of influenza vaccination and intentions to accept influenza and COVID-19 vaccination were collected. Their relationship with work-related and other factors were examined using multiple multinomial logistic regressions.ResultsResponses from 806 participants were retrieved. More nurses changed from vaccination refusal to hesitancy or acceptance than those changed from acceptance to vaccination hesitancy or refusal (15.5% vs 6.8% among all participants, P < 0.001). 40.0% participants intended to accept COVID-19 vaccination, and those in private sector (OR: 1.67, 95%CI: 1.11–2.51), with chronic conditions (OR: 1.83, 95%CI: 1.22–2.77), encountering with suspected or confirmed COVID-19 patients (OR: 1.63, 95%CI: 1.14–2.33), accepted influenza vaccination in 2019 (OR: 2.03, 95%CI: 1.47–2.81) had higher intentions to accept it. Reasons for refusal and hesitation for COVID-19 vaccination included “suspicion on efficacy, effectiveness and safety”, “believing it unnecessary”, and “no time to take it”.ConclusionWith a low level of COVID-19 acceptance intentions and high proportion of hesitation in both influenza and COVID-19 vaccination, evidence-based planning are needed to improve the uptake of both vaccinations in advance of their implementation. Future studies are needed to explore reasons of change of influenza vaccination acceptance, look for actual behaviour patterns of COVID-19 vaccination acceptance and examine effectiveness of promotion strategies.     

Comparison of adjuvants to optimize influenza neutralizing antibody responses

Seasonal influenza vaccines represent a positive intervention to limit the spread of the virus and protect public health. Yet continual influenza evolution and its ability to evade immunity pose a constant threat. For these reasons, vaccines with improved potency and breadth of protection remain an important need. We previously developed a next-generation influenza vaccine that displays the trimeric influenza hemagglutinin (HA) on a ferritin nanoparticle (NP) to optimize its presentation. Similar to other vaccines, HA-nanoparticle vaccine efficacy is increased by the inclusion of adjuvants during immunization. To identify the optimal adjuvants to enhance influenza immunity, we systematically analyzed TLR agonists for their ability to elicit immune responses. HA-NPs were compatible with nearly all adjuvants tested, including TLR2, TLR4, TLR7/8, and TLR9 agonists, squalene oil-in-water mixtures, and STING agonists. In addition, we chemically conjugated TLR7/8 and TLR9 ligands directly to the HA-ferritin nanoparticle. These TLR agonist-conjugated nanoparticles induced stronger antibody responses than nanoparticles alone, which allowed the use of a 5000-fold-lower dose of adjuvant than traditional admixtures. One candidate, the oil-in-water adjuvant AF03, was also tested in non-human primates and showed strong induction of neutralizing responses against both matched and heterologous H1N1 viruses. These data suggest that AF03, along with certain TLR agonists, enhance strong neutralizing antibody responses following influenza vaccination and may improve the breadth, potency, and ultimately vaccine protection in humans.