Future Vaccination Strategies Research Articles

Safety and Immunogenicity of SARS-CoV-2 Vaccines in People Living With HIV: A Systematic Review and Meta-analysis of Real-World Studies

Abstract The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with HIV (PLWH) in real-world studies remain controversial. Thus, we conducted a comprehensive systematic review and meta-analysis to address this issue. Data search were conducted from PubMed, Web of Science and EMBASE. Adverse events following vaccination, the risk ratio (RR) of SARS-CoV-2–specific IgG seroconversion and the level of anti–SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group. A total of 10,582 PLWH from 22 studies were included. In our analysis, the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy controls. However, there was a statistical difference after the second dose (RR, 0.83; 95% CI, 0.71–0.98). The seroconversion rate of SARS-CoV-2 IgG antibodies in PLWH was significantly lower than that in the healthy control group (RR, 0.94; 95% CI, 0.89–0.98; I 2 = 80%, P < 0.01). The anti–SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than those in the healthy control group (RR, 0.91; 95% CI, 0.85–0.98; I 2 = 81%, P < 0.01). The safety and tolerance of COVID-19 vaccines in PLWH are acceptable. However, their immunogenicity may be impaired to a certain extent, characterized by a lower IgG seroconversion rate and neutralizing antibody titers compared with healthy individuals. These findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.

Disruptions to and Innovations in HPV Vaccination Strategies within Safety-Net Healthcare Settings Resulting from the COVID-19 Pandemic.

The COVID-19 pandemic disrupted healthcare delivery within safety-net settings. Barriers to and facilitators of human papillomavirus (HPV) vaccination during the pandemic can inform future HPV vaccine strategies for underserved communities. Qualitative interviews (n = 52) between December 2020 and January 2022 in Los Angeles and New Jersey were conducted with providers, clinic leaders, clinic staff, advocates, payers, and policy-level representatives involved in the HPV vaccine process. Using the updated Consolidated Framework for Implementation Research we identified (1) outer setting barriers (i.e., vaccine hesitancy driven by social media, political views during the pandemic) and facilitators (e.g., partnerships); (2) inner setting clinic facilitators (i.e., motivation-driven clinic metrics, patient outreach, vaccine outreach events); (3) individual characteristics such as patient barriers (i.e., less likely to utilize clinic services during the pandemic and therefore, additional outreach to address missed vaccine doses are needed); (4) innovations in HPV vaccination strategies (i.e., clinic workflow changes to minimize exposure to COVID-19, leveraging new community partnerships (e.g., with local schools)); and (5) implementation strategies (i.e., multisectoral commitment to HPV goals). Pandemic setbacks forced safety-net settings to develop new vaccine approaches and partnerships that may translate to new implementation strategies for HPV vaccination within local contexts and communities.

Neutralization against Omicron subvariants after BA.5/BF.7 breakthrough infection weakened as virus evolution and aging despite repeated prototype-based vaccination1

ABSTRACT Background: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it’s urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. Method: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. Results: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual’s humoral responses against the latest Omicron subvariants. Conclusions: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan.

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.

Socio-demographic characteristics associated with COVID-19 vaccination uptake in Switzerland: longitudinal analysis of the CoMix study

BackgroundVaccination is an effective strategy to reduce morbidity and mortality from coronavirus disease 2019 (COVID-19). However, the uptake of COVID-19 vaccination has varied across and within countries. Switzerland has had lower levels of COVID-19 vaccination uptake in the general population than many other high-income countries. Understanding the socio-demographic factors associated with vaccination uptake can help to inform future vaccination strategies to increase uptake.MethodsWe conducted a longitudinal online survey in the Swiss population, consisting of six survey waves from June to September 2021. Participants provided information on socio-demographic characteristics, history of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), social contacts, willingness to be vaccinated, and vaccination status. We used a multivariable Poisson regression model to estimate the adjusted rate ratio (aRR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake.ResultsWe recorded 6,758 observations from 1,884 adults. For the regression analysis, we included 3,513 observations from 1,883 participants. By September 2021, 600 (75%) of 806 study participants had received at least one vaccine dose. Participants who were older, male, and students, had a higher educational level, household income, and number of social contacts, and lived in a household with a medically vulnerable person were more likely to have received at least one vaccine dose. Female participants, those who lived in rural areas and smaller households, and people who perceived COVID-19 measures as being too strict were less likely to be vaccinated. We found no significant association between previous SARS-CoV-2 infections and vaccination uptake.ConclusionsOur results suggest that socio-demographic factors as well as individual behaviours and attitudes played an important role in COVID-19 vaccination uptake in Switzerland. Therefore, appropriate communication with the public is needed to ensure that public health interventions are accepted and implemented by the population. Tailored COVID-19 vaccination strategies in Switzerland that aim to improve uptake should target specific subgroups such as women, people from rural areas or people with lower socio-demographic status.

Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a one-year follow-up of the prospective clinical trial COVAXID.

Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection. In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARS-CoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659). The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication. The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies. The present studies were supported by grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and Karolinska Institutet.

Epidemiological impacts of attenuated African swine fever virus circulating in wild boar populations

African swine fever virus (ASFV) genotype II has been present in wild boar in the European Union since 2014. Control measures have reduced the incidence of the ASF, but highly virulent as well as attenuated ASFV strains continue to circulate. We present the intraherd epidemiological parameters of low and highly virulent ASFV in wild boar from experimental data, and for the first time, evaluate the impact of attenuated strain circulation through unique deterministic compartmental model simulations under various potential scenarios and hypotheses.Using an estimated PCR infectious threshold of TPCR = 36.4, we obtained several transmission parameters, like an Rx (experimental intraherd R0) value of 4.5. We also introduce two novel epidemiological parameters: infectious power and resistance power, which indicate the ability of animals to transmit the infection and the reduction in infectiousness after successive exposures to varying virulence strains, respectively.The presence of ASFV attenuated strains results in 4–17% of animals either remaining in a carrier state or becoming susceptible again when exposed to highly virulent ASFV for more than two years. The timing between exposures to viruses of different virulence also influences the percentage of animals that die or remain susceptible.The findings of this study can be utilized in epidemiological modelling and provide insight into important risk situations that should be considered for surveillance and future potential ASF vaccination strategies in wild boar.

Health effects of routine measles vaccination and supplementary immunisation activities in 14 high-burden countries: a Dynamic Measles Immunization Calculation Engine (DynaMICE) modelling study

WHO recommends at least 95% population coverage with two doses of measles-containing vaccine (MCV). Most countries worldwide use routine services to offer a first dose of measles-containing vaccine (MCV1) and later, a second dose of measles-containing vaccine (MCV2). Many countries worldwide conduct supplementary immunisation activities (SIAs), offering vaccination to all people in a specific age range irrespective of previous vaccination history. We aimed to estimate the relative effects of each dose and delivery route in 14 countries with high measles burden. We used an age-structured compartmental dynamic model, the Dynamic Measles Immunization Calculation Engine (DynaMICE), to assess the effects of different vaccination strategies on measles susceptibility and burden during 2000-20 in 14 countries with high measles incidence (containing 53% of the global birth cohort and 78% of the global measles burden). Country-specific routine MCV1 and MCV2 coverage data during 1980-2020 were obtained from the WHO and UNICEF Estimates of National Immunization Coverage database for all modelled countries and SIA data were obtained from the WHO summary of measles and rubella SIAs. We estimated the incremental health effects of different vaccination strategies using prevented cases of measles and deaths from measles and their efficiency using the incremental number needed to vaccinate (NNV) to prevent an additional measles case. Compared with no vaccination, MCV1 implementation was estimated to have prevented 824 million cases of measles and 9·6 million deaths from measles, with a median NNV of 1·41 (IQR 1·35-1·44). Adding routine MCV2 to MCV1 was estimated to have prevented 108 million cases and 404 270 deaths, whereas adding SIAs to MCV1 was estimated to have prevented 256 million cases and 4·4 million deaths. Despite larger incremental effects, adding SIAs to MCV1 (median incremental NNV 6·02, 5·30-7·68) showed reduced efficiency compared with adding routine MCV2 (5·41, 4·76-6·11). Vaccination strategies, including non-selective SIAs, reach a greater proportion of children who are unvaccinated and reduce measles burden more than MCV2 alone, but efficiency is lower because of the wide age range targeted by SIAs. This analysis provides information to help improve the health effects and efficiency of measles vaccination strategies. The interplay between MCV1, MCV2, and SIAs should be considered when planning future measles vaccination strategies. Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Factors influencing Australian nursing and midwifery students COVID-19 vaccination intentions

BackgroundVaccination for COVID-19 has become a cornerstone management plan for many countries. Australian state governments made vaccinations mandatory for all healthcare workers. Despite evidence on the important role vaccines hold in preventing or decreasing serious disease, there have been many nurses and midwives who have demonstrated vaccine hesitancy. This hesitancy has also been present in undergraduate nursing and midwifery students. The aim of this study was to explore factors influencing Australian nursing and midwifery students' intentions towards receiving the COVID-19 vaccine; identify the barriers and facilitators to obtaining the COVID-19 vaccine; and understand students' perceptions of mandating the COVID-19 vaccine and identify any impact on their studies.. MethodsCross-sectional mixed method study utilising an online survey platform. Data were analysed using binomial and multinomial logistic regression through Statistical Package for the Social Sciences. A content analysis was completed for the qualitative data. ResultsThere were 715 participants and 556 who completed the survey in full. Nurses made up the majority of participants (n = 409), 133 participants were midwives and 30 were in dual nursing/midwifery programs. Education and communication were identified as two major factors that facilitate vaccine acceptance. ConclusionsVaccines are integral in the prevention of contracting COVID-19 or reducing the severity of the symptoms. However, many nursing and midwifery students have shown reluctance towards getting vaccinated. The mandate to be vaccinated to attend clinical placement has led to the inability of some students to complete their course. The findings from this study are valuable in informing the future COVID-19 vaccination strategies and improving vaccine acceptance. COVID-19 remains a global health risk and therefore further research is needed of vaccine acceptance amongst the future health workforces. It is crucial knowledge for policy makers and healthcare services as they plan for any future pandemics and implement Australia's national vaccine strategy.

Serologic Response to SARS-CoV-2 Vaccine in Patients with Breast Cancer

Background: Our study aimed to measure effectiveness of Anti-S1 RBD (receptor binding domain) IgG Antibody levels against SARS (severe acute respiratory syndrome) Cov-2 in breast cancer patients and compare them with healthy participants.
 Methods: This prospective cross-sectional, single-center study was designed to evaluate Anti-S1 RBD IgG antibody levels following SARS-CoV-2 vaccination in 54 breast cancer patients and 56 healthy controls without cancer diagnosis.
 Results: Anti-S1 RBD IgG antibody test was positive in 79.6% (43/54) of breast cancer patients, in 92.9% (52/56) of participants in the control group (p=0.054) and, 63.3% in breast cancer patients who were on chemotherapy+/-molecularly targeted therapy following at least two doses of vaccinations. Hybrid vaccination (use of two different types of vaccines) and more than two doses of vaccinations were associated with higher antibody titers both in patient and control groups. Median time to vaccination was 123 days (8-427) in the entire group and was significantly associated with antibody titer. Among breast cancer patients, type and frequency of vaccination, age and use of cytotoxic therapies were significantly associated with the magnitude of antibody response to SARS-CoV-2 vaccination in our study.
 Conclusion: Breast cancer patients developed a lower antibody response to vaccination against COVID-19 in comparison to healthy subjects. Clinical and treatment related factors might help in tailoring future vaccination strategies for specific subsets of breast cancer patients.

A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

Поширеність антитіл до SARS-CoV-2 у дітей та підлітків: одноцентрове дослідження

Despite the fact that children with COVID-19 are usually asymptomatic or mild, infection with SARS-CoV-2 is more likely to lead to the development of an antibody response. Understanding humoral immunity to SARS-CoV-2, including in children, is critical for future public health and vaccination strategies. Children with chronic diseases deserve special attention. Purpose - to study the prevalence of positive antibodies to SARS-CoV-2 in children and adolescents who were in paediatric hospital without signs of viral disease to develop future healthcare strategies. Materials and methods. In 32 children aged 6-17 years (14 (43.8%) boys and 16 (56.2%) girls) quantitative determination of IgG antibodies to SARS-CoV-2 in blood serum was carried out by enzyme immunoassay using commercial SARS-CoV-2 S1\RBD IgG Ab ELISA (TECAN, IBL International GmbH, Germany). Results. The majority (n=27, 84.4%) of children had a positive level of class G antibodies to SARS-CoV-2. 7 (25.9%) children had a positive PCR test in their anamnesis, 6 (18.8%) persons provided information about the infection transmitted by family members. Clinical manifestations characteristic of SARS-CoV-19 were present in 2 (7.4%) children. Parents of 18 (66.7%) children claimed that their children had no symptoms of COVID-19, while family members of 6 (33.3%) children had cases of the disease. All children (n=6, 18.8%) who were vaccinated with two doses of Comirnaty® vaccine had positive IgG antibodies to SARS-CoV-2. Antibodies to SARS-CoV-2 were absent in 5 (15.4%) people, all of them were patients with type 1 diabetes. Conclusions. The study of the prevalence of antibodies to SARS-CoV-2 provides important information about circulating antibodies against SARS-CoV-2 in children and adolescents, in particular those with chronic diseases. The obtained results showed the predominant seropositivity of children, which is formed regardless of the clinical manifestations of the disease. A high level of antibodies under the conditions of revaccination confirms the benefit of revaccination of children to strengthen memory formation. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

No Difference in the Prevalence of HIV-1 gag Cytotoxic T-Lymphocyte-Associated Escape Mutations in Viral Sequences from Early and Late Parts of the HIV-1 Subtype C Pandemic in Botswana.

HIV is known to accumulate escape mutations in the gag gene in response to the immune response from cytotoxic T lymphocytes (CTLs). These mutations can occur within an individual as well as at a population level. The population of Botswana exhibits a high prevalence of HLA*B57 and HLA*B58, which are associated with effective immune control of HIV. In this retrospective cross-sectional investigation, HIV-1 gag gene sequences were analyzed from recently infected participants across two time periods which were 10 years apart: the early time point (ETP) and late time point (LTP). The prevalence of CTL escape mutations was relatively similar between the two time points-ETP (10.6%) and LTP (9.7%). The P17 protein had the most mutations (9.4%) out of the 36 mutations that were identified. Three mutations (A83T, K18R, Y79H) in P17 and T190A in P24 were unique to the ETP sequences at a prevalence of 2.4%, 4.9%, 7.3%, and 5%, respectively. Mutations unique to the LTP sequences were all in the P24 protein, including T190V (3%), E177D (6%), R264K (3%), G248D (1%), and M228L (11%). Mutation K331R was statistically higher in the ETP (10%) compared to the LTP (1%) sequences (p < 0.01), while H219Q was higher in the LTP (21%) compared to the ETP (5%) (p < 0.01). Phylogenetically, the gag sequences clustered dependently on the time points. We observed a slower adaptation of HIV-1C to CTL immune pressure at a population level in Botswana. These insights into the genetic diversity and sequence clustering of HIV-1C can aid in the design of future vaccine strategies.

Single-cell cloning of NK cells from rhesus macaques: a new methodology for in-depth analysis of MHC-E-dependent adaptive functions

Abstract Natural killer (NK) cells provide rapid and robust responses against a wide range of viral infections. More recently, multiple studies have shown that subsets of NK cells are also capable of antigen-specific recall to eliminate infected cells. In humans and nonhuman primates (NHP), antigen-specific memory NK cell responses can at least be partially delineated by expression of NKG2C, a ligand for MHC-E. Due to MHC-E limited polymorphism, MHC-E-presented viral antigens may induce universally antigen-specific memory NK cells. To study antigen-specific NK cells in NHP, we developed a new in vitromethod to clonally expand single rhesus macaque NK cells (rhNKCL) from blood and spleen. To define the effector functions of rhNKCL, we used a calcein acetoxymethyl ester (CAM) cytotoxicity assay and intracellular staining assay in combination with K562 cell lines or autologous BLCL as targets. We also identified, by in silicomethodology, peptides from influenza, SIV, and SARS-CoV-2 viruses predicted to display strong binding to MHC-E. Our procedure showed for the first-time clonal expansion of single rhesus macaque NK cells. We observed a conserved NHP NK cell phenotype of CD3 −NKG2A/C +CD16 +CD56 +following expansion with expression of additional NK cell surface receptors CD8, NKp80, and NKG2D. Upon stimulation with K562 cells, rhNKCL effector functions (cytotoxicity, CD107a, IFNγ, TNFα) were like primary NK cells. Altogether, this new method of single-cell cloning in rhesus macaques could provide key information about antigen-specific NK cells, including epigenetic, metabolic, transcriptional, and phenotypic profiles, which could be exploited to further enhance antiviral NK cell activity in future vaccine strategies or cell therapies. Supported by grants from NIH (R01 AI158516, R01 DK130472, R01 AI161010, NIH-funded BEAT-HIV Martin Delaney Collaboratory to cure HIV-1 infection by Combination Immunotherapy UM1 AI164570).

High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants.

The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.

COVID-19 Vaccine Acceptance and Hesitancy in Health Care Workers in Somalia: Findings from a Fragile Country with No Previous Experience of Mass Adult Immunization.

Coverage of COVID-19 vaccines in Somalia remains low, including among health workers. This study aimed to identify factors associated with COVID-19 vaccine hesitancy among health workers. In this cross-sectional, questionnaire-based study, 1476 health workers in government and private health facilities in Somalia's federal member states were interviewed face-to-face about their perceptions of and attitudes toward COVID-19 vaccines. Both vaccinated and unvaccinated health workers were included. Factors associated with vaccine hesitancy were evaluated in a multivariable logistic regression analysis. Participants were evenly distributed by sex, and their mean age was 34 (standard deviation 11.8) years. The overall prevalence of vaccine hesitancy was 38.2%. Of the 564 unvaccinated participants, 39.0% remained hesitant. The factors associated with vaccine hesitancy were: being a primary health care worker (adjusted odds ratio (aOR) = 2.37, 95% confidence interval (CI): 1.15-4.90) or a nurse (aOR = 2.12, 95% CI: 1.05-4.25); having a master's degree (aOR = 5.32, 95% CI: 1.28-22.23); living in Hirshabelle State (aOR = 3.23, 95% CI: 1.68-6.20); not having had COVID-19 (aOR = 1.96, 95% CI: 1.15-3.32); and having received no training on COVID-19 (aOR = 1.54, 95% CI: 1.02-2.32). Despite the availability of COVID-19 vaccines in Somalia, a large proportion of unvaccinated health workers remain hesitant about being vaccinated, potentially influencing the public's willingness to take the vaccine. This study provides vital information to inform future vaccination strategies to achieve optimal coverage.

Feeding Spray-Dried Porcine Plasma to Pigs Improves the Protection Afforded by the African Swine Fever Virus (ASFV) BA71∆CD2 Vaccine Prototype against Experimental Challenge with the Pandemic ASFV-Study 2.

This study aimed to evaluate the effects of feeding spray-dried porcine plasma (SDPP) on the protection afforded by the BA71∆CD2 African swine fever virus (ASFV) vaccine prototype. Two groups of pigs acclimated to diets without or with 8% SDPP were intranasally inoculated with 105 plaque-forming units (PFU) of live attenuated ASFV strain BA71∆CD2 and, three weeks later, left in direct contact with pigs infected with the pandemic Georgia 2007/01 ASFV strain. During the post-exposure (pe) period, 2/6 from the conventional diet group showed a transient peak rectal temperature >40.5 °C before day 20 pe, and some tissue samples collected at 20 d pe from 5/6 were PCR+ for ASFV, albeit showing Ct values much higher than Trojan pigs. Interestingly, the SDPP group did not show fever, neither PCR+ in blood nor rectal swab at any time pe, and none of the postmortem collected tissue samples were PCR+ for ASFV. Differential serum cytokine profiles among groups at vaccination, and a higher number of ASFV-specific IFNϒ-secreting T cells in pigs fed with SDPP soon after the Georgia 2007/01 encounter, confirmed the relevance of Th1-like responses in ASF protection. We believe that our result shows that nutritional interventions might contribute to improving future ASF vaccination strategies.

Protective Effect of Inactivated COVID-19 Vaccines against Omicron BA.2 Infection in Guangzhou: A Test-Negative Case-Control Real-World Study

This study aims to explore the relationship between the doses of inactivated COVID-19 vaccines received and SARS-CoV-2 Omicron infection in the real-world setting, so as to preliminarily evaluate the protective effect induced by COVID-19 vaccination. We conducted a test-negative case-control study and recruited the test-positive cases and test-negative controls in the outbreak caused by Omicron BA.2 in April 2022 in Guangzhou, China. All the participants were 3 years and older. The vaccination status between the case group and the control group was compared in the vaccinated and all participants, respectively, to estimate the immune protection of inactivated COVID-19 vaccines. After adjusting for sex and age, compared with a mere single dose, full vaccination of inactivated COVID-19 vaccines (OR = 0.191, 95% CI: 0.050 to 0.727) and booster vaccination (OR = 0.091, 95% CI: 0.011 to 0.727) had a more superior protective effect. Compared with one dose, the second dose was more effective in males (OR = 0.090), as well as two doses (OR = 0.089) and three doses (OR = 0.090) among individuals aged 18-59. Whereas, when compared with the unvaccinated, one dose (OR = 7.715, 95% CI: 1.904 to 31.254) and three doses (OR = 2.055, 95% CI: 1.162 to 3.635) could contribute to the increased risk of Omicron infection after adjusting for sex and age. Meanwhile, by contrast with unvaccinated individuals, the result of increased risk was also manifested in the first dose in males (OR = 12.400) and one dose (OR = 21.500), two doses (OR = 1.890), and a booster dose (OR = 1.945) in people aged 18-59. In conclusion, the protective effect of full and booster vaccination with inactivated COVID-19 vaccines exceeded the incomplete vaccination, of which three doses were more effective. Nevertheless, vaccination may increase the risk of Omicron infection compared with unvaccinated people. This may result from the transmission traits of BA.2, the particularity and stronger protection awareness of the unvaccinated population, as well as the ADE effect induced by the decrease of antibody titers after a long time of vaccination. It is crucial to explore this issue in depth for the formulation of future COVID-19 vaccination strategies.

Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies—YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.