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"Cross Protection"
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Increase in H5N1 vaccine antibodies confers cross-neutralization of highly pathogenic avian influenza H5N1
H5N1, a highly pathogenic avian influenza virus, presents pandemic risks due to its ability to adapt and spread among mammalian species. Vaccination may control its spread, but the effectiveness of existing H5N1 vaccines against circulating strains, especially clade 2.3.4.4b, remains uncertain. In this study, we assess neutralizing antibody responses to global circulating H5N1 strains, using sera from individuals vaccinated with an inactivated H5N1 vaccine (NCT00535665). Neutralization is measured against 17 pseudoviruses, representing circulating and vaccine H5 strains. Our results indicate that broad protective effects are observed only when high antibody titers are achieved by vaccination. Correlation analysis estimates that a pseudovirus-based neutralization titer of at least 1:980 is required to achieve a cross-protection rate above 60%. The findings suggest that the current H5N1 vaccine can elicit cross-neutralization of circulating H5N1 strains, if high antibody titers are achieved. Until updated H5N1 vaccines are developed, this vaccine may serve as a bridging measure.
Effectiveness of existing H5N1 vaccines against circulating influenza strains remains largely unknow. Here, the authors test neutralization activity of sera from individuals vaccinated with an inactivated H5N1 vaccine against 17 pseudoviruses and suggest that high vaccine-induced antibody level likely provide cross-protection against circulating H5N1 strains.
Journal Article
Induction of trained immunity by influenza vaccination - impact on COVID-19
Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity , has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.
Journal Article
A New Era for Mild Strain Cross-Protection
Societal and environmental pressures demand high-quality and resilient cropping plants and plant-based foods grown with the use of low or no synthetic chemical inputs. Mild strain cross-protection (MSCP), the pre-immunization of a plant using a mild strain of a virus to protect against subsequent infection by a severe strain of the virus, fits with future-proofing of production systems. New examples of MSCP use have occurred recently. New technologies are converging to support the discovery and mechanism(s) of action of MSCP strains thereby accelerating the popularity of their use.
Journal Article
Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population
Abstract
Background
Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended for 5 years because of safety concerns. While no scientific evidence exists to substantiate these concerns, one reason given for not reinstating recommendations is the lack of reliable vaccine effectiveness (VE) data in a Japanese population. This study reports the VE of the bivalent HPV vaccine in Japanese women aged 20–22 years.
Methods
During cervical screening between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and provided data about their sexual history. Estimates of VE for vaccine-targeted HPV type 16 (HPV16) and 18 and cross-protection against other types were calculated.
Results
Overall, 2197 women were tested, and 1814 were included in the analysis. Of these, 1355 (74.6%) were vaccinated, and 1295 (95.5%) completed the 3-dose schedule. In women sexually naive at vaccination, the pooled VEs against HPV16 and 18 and for HPV31, 45, and 52 were 95.5% (P < .01) and 71.9% (P < .01), respectively. When adjusted for number of sex partners and birth year, pooled VEs were 93.9% (P = .01) and 67.7% (P = .01) for HPV16 and 18 and HPV31, 45, and 52, respectively.
Conclusions
The bivalent HPV vaccine is highly effective against HPV16 and 18. Furthermore, significant cross-protection against HPV31, 45, and 52 was demonstrated and sustained up to 6 years after vaccination. These findings should reassure politicians about the VE of bivalent HPV vaccine in a Japanese population.
Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended. In this study, bivalent HPV vaccine is highly effective against HPV types 16 (HPV16) and 18, and significant cross-protection against HPV31, 45, and 52 was demonstrated. These findings should reassure politicians of vaccine effectiveness in a Japanese population.
Journal Article
Systematic literature review of cross-protective effect of HPV vaccines based on data from randomized clinical trials and real-world evidence
•Cross-protective effect of HPV vaccines against non-vaccine types is inconsistent.•Cross-protection does not cover all HPV types included by the nonavalent vaccine.•Bivalent and quadrivalent vaccines’ cross-protection is partial and wanes over time.•Direct protection afforded by HPV types included in HPV vaccines is complete and durable.
The extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies.
PubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts.
Data from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% [95% CI: 27.6 to 83.9] to 79.1% [97.7% CI: 27.6 to 95.9] for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% [15.3–66.4]; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines.
RCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established.
Journal Article
Omicron infection enhances Delta antibody immunity in vaccinated persons
The extent to which Omicron infection
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, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3–9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19–27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.
A study quantifying the neutralization of severe acute respiratory syndrome coronavirus 2 variants in individuals infected with Omicron/BA.1 shows that vaccinated individuals previously infected with Omicron have enhanced protection against reinfection with current variants, \\including Omicron/BA.2, while Omicron/BA.1 infected unvaccinated individuals have limited protection.
Journal Article
Cross-reactive immunity within pneumococcal serogroups: Implications for next-generation vaccine development
This study aims to investigate within-serogroup cross-reactive immunity among pneumococcal serotypes using inhibition opsonophagocytic assays (OPA). The findings provide immunologic insights into serotype-replacement dynamics with implications for the design of future pneumococcal vaccines.
Pooled sera were prepared from 24 adults aged ≥40 years: Pool 1 (PCV13/PPSV23 recipients), Pool 2 (PCV20 recipients), and Pool 3 (PCV21 recipients). Cross-reactivity was examined across five major serogroups (6, 9, 15, 19, 23) by measuring residual OPA titers after adsorption with homologous or heterologous inactivated pneumococcal strain.
Cross-reactivity varied by serogroup. In serogroup 6, 6A induced broad cross-protection against 6B and 6C, whereas 6D showed only homologous reactivity. In serogroup 15, inhibition OPA revealed inconsistent cross-reactivity between serotypes 15B and 15C, with only limited cross-reactivity observed for 15A. Pooled sera from PCV21 recipients (containing 15A and 15C) demonstrated pronounced heterologous inhibition toward 15B. In serogroup 19, cross-reactivity between 19A and 19F was partial and asymmetric. Heterologous adsorption showed negligible reductions in OPA titers for serogroups 9 and 23.
The inhibition OPA enabled a precise assessment of serogroup-level cross-reactive immunity, revealing heterogeneous patterns of cross-reactivity. These findings underscore the need for careful serotype selection and epitope evaluation in next-generation vaccine formulations.
Journal Article