Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

With the onset of the COVID-19 pandemic 4 years ago, viral sequencing continues to document numerous individual mutations in the viral spike protein across many variants. To determine the ability of vaccine-mediated humoral immunity to combat continued SARS-CoV-2 evolution, we construct a comprehensive panel of pseudoviruses harboring each individual mutation spanning 4 years of the pandemic to understand the fitness cost and resistance benefits of each. These efforts identify numerous mutations that escape from vaccine-induced humoral immunity.

Comparison of immunogenicity of adjuvanted and high dose influenza vaccination in long-term care facility residents.

Background: The CDC recommends the more immunogenic adjuvanted and high-dose flu vaccines over standard-dose, non-adjuvanted vaccines for individuals above 65 years old. The current study compares adjuvanted trivalent inactivated flu vaccine (aTIV, FLUAD) versus high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met non-inferiority standards for older long-term care facility (LTCF) residents.

Methods: We collected blood from long-term care facility residents participating in a randomized 1:1 active control trial comparing MF59C.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

Background: Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents.

Methods: We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine.

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers.

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW).

Longitudinal Analysis of Nursing Home Residents' T-Cell Responses After SARS-CoV-2 mRNA Vaccinations Shows Influence of Biological Sex and Infection History.

Background: Vaccines and vaccine boosting have blunted excess morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older nursing home residents (NHR). However, the impact of repeated vaccination on the T-cell response based on biological sex and prior infection of NHR remain understudied.

Methods: We examined T-cell responses to SARS-CoV-2 mRNA vaccines in a cohort of NHR and healthcare workers (HCW) over 2 years.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera.

Effective and targeted latency reversal in CD4 T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection.

To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most "latency reversal" agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5-20 years on stable cART, HLP could target CD4 T cells harbouring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs.

Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation.

Background: The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of human immune cells.

Methods: We stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells.

The association between influenza vaccine effectiveness and egg-based manufacturing technology: literature review and US expert consensus.

Background: Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses.

impairs human memory CD4 T cell recognition of M2 but not M1-like macrophages.

Direct recognition of (Mtb)-infected cells is required for protection by CD4 T cells. While impaired T cell recognition of Mtb-infected macrophages was demonstrated in mice, data are lacking for humans. Using T cells and monocyte-derived macrophages (MDMs) from individuals with latent Mtb infection (LTBI), we quantified the frequency of memory CD4 T cell activation in response to autologous MDMs infected with virulent Mtb.

Rheumatoid arthritis and older age are associated with lower humoral and cellular immune response to primary series COVID-19 mRNA vaccine.

Objective: People with autoimmune disease have worse COVID-19 infection-related outcomes, lower antibody responses to COVID-19 vaccine, and higher rates of breakthrough infection. Immunosuppressive medications used to treat rheumatoid arthritis (RA) are associated with lower COVID-19 vaccine responses, though independent contributions of comorbidities, T-cell immunity, and age are less clear. We sought to test the hypothesis that RA, immunosuppressive medications used to treat RA, and older age, contribute to reduced B and T cell response to COVID-19 vaccine.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.

Humoral and Cellular Immunity Induced by Adjuvanted and Standard Trivalent Influenza Vaccine in Older Nursing Home Residents.

Background: Despite wide use of adjuvanted influenza vaccine in nursing home residents (NHR), little immunogenicity data exist for this population.

Methods: We collected blood from NHR (n = 85) living in nursing homes participating in a cluster randomized clinical trial comparing MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) with nonadjuvanted vaccine (TIV) (parent trial, NCT02882100). NHR received either vaccine during the 2016-2017 influenza season.

Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection.

Background: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined.

Methods: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing.

Results: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ.

Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers.

Background: Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with antibody (Ab) titers after primary and booster BNT162b2 mRNA vaccinations in healthcare workers (HCWs) and nursing home (NH) residents.

Methods: Nursing home residents ( = 143) and HCWs ( = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.

Vaccines for the Prevention of Coronavirus Disease 2019 in Older Adults.

Institutionalized and community-dwelling older adults have been greatly impacted by the coronavirus disease 2019 (COVID-19) pandemic with increased morbidity and mortality. The advent of vaccines and their widespread use in this population has brought about a dramatic turnaround in COVID-19 outcomes. The immunogenicity and effectiveness of the various vaccine options worldwide are discussed.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks.

SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine - Ohio and Rhode Island, September-November 2022.

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.

High-dose influenza vaccines for the prevention of hospitalization due to cardiovascular events in older adults in the nursing home: Post-hoc analysis of a cluster-randomized trial.

Older adults are at high risk of major acute cardiovascular events (MACE) linked to influenza illness andpreventable by influenza vaccination. It is unknown whether high-dose vaccine might incrementally reduce the risk of MACE.We conducted a post-hoc analysis of data collected from a pragmatic cluster randomized study of 823 nursing homes (NH) randomized to standard-dose (SD) or high-dose (HD) influenza vaccine in the 2013-14 season.