IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2.0 were observed. Grade 1/2 injection site reactions were observed in five of seven patients. IgG and IgM responses to Emm55 peptides and known melanoma antigens were seen in the peripheral blood, suggesting that IFx-Hu2.0 acts as an individualized “in situ vaccine.” Three of four patients previously refractory to anti-PD1 experienced clinical benefit upon subsequent anti-PD1–based treatment. Therefore, this approach is feasible, and clinical/correlative outcomes warrant further investigation for treating patients with metastatic melanoma with an immune priming agent.

Background: Compared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS‐CoV‐2 infection. The immune response to a two‐dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 μg) of mRNA‐1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days. Methods: The mRNA‐1273 vaccine was administered ∼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme‐linked immunosorbent assay [ELISA]) were assessed 28 days post‐dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post‐dose three. Fisher exact or X ² tests were used to compare SARS‐CoV‐2 antibody positivity rates, and paired t ‐tests were used to compare SARS‐CoV‐2 antibody geometric mean titers (GMTs) across different time intervals. Results: Among 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA‐1273 increased the percentage of patients seropositive for SARS‐CoV‐2 antibody from 81.7% pre‐dose three to 94.4% 28 days post‐dose three. GMTs increased 19.0‐fold (15.8‐22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post–dose three, respectively. Antibody responses after dose three were reduced among those who received anti‐CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS‐CoV‐2 antibody pre‐dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment‐emergent events within 28 days were very rare (<2%). Conclusion: Dose three of the mRNA‐1273 vaccine was well‐tolerated and augmented SARS‐CoV‐2 seropositivity in cancer patients, especially those who did not seroconvert post–dose two or whose GMTs significantly waned post–dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA‐1273 vaccine, suggesting that timely access to boosters is important for this population.

SARS-CoV-2 Period Seroprevalence, Florida, USA

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal–Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

Human papillomavirus (HPV)-related oropharyngeal cancer arises from persistent high-risk HPV (HR-HPV) oral infection. Smoking is a risk factor for oral HPV, but alcohol's role is unclear. We investigated the association between alcohol consumption and oral HPV infection. This cross-sectional analysis used baseline data from the HIM Study. Oral HPV was detected with SPF10 PCR-DEIA-LiPA25 on oral gargle specimens. Associations between alcohol consumption and oral HPV were assessed using adjusted logistic regression models, exploring effect modification by smoking. Among 3121 males (median age 33 years, interquartile range [IQR] 25, 41), 39% were from Brazil (n = 1229), 32% from Mexico (n = 1014), and 28% from the United States (n = 878); 76% (n = 2365) reported alcohol use in the past month (median 8 drinks, IQR 0, 24). Oral HPV was detected in 20% (n = 469) participants reporting alcohol use, including 6.1% (n = 145) with HR-HPV and 14% (n = 324) low-risk HPV (LR-HPV). HR-HPV detection increased with alcohol intake, peaking at 7.6% (n = 75) among those consuming ≥16 drinks/month (p = 0.005). Consuming ≥16 drinks/month was independently associated with HR-HPV after adjustment (adjusted odd ratio [aOR] 1.60, 95% confidence interval [CI] 1.07, 2.40), whereas consuming 3-15 drinks was not (aOR 1.15, 95% CI: 0.76, 1.76). Exploratory stratified analyses showed aOR 2.57 (95% CI: 1.37, 4.96) in males who had never smoked and 1.12 (95% CI: 0.67, 1.88) in those who currently or formerly smoked, with no evidence of effect modification. Higher monthly alcohol consumption was modestly associated with oral HR-HPV in this cross-sectional analysis; longitudinal studies are needed to assess extension to oral HPV persistence, a recognized precursor of cancer. National Institute of Health, American Cancer Society.

We conducted a prospective study to evaluate immune responses to SARS-CoV-2 in oncology workers in which we collected blood and clinical data every 6 months. Spike-specific CD4⁺ T-cells and immunoglobulin G responses were measured using interferon-gamma enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay, respectively. Sixty (81%) vaccinated and 14 (19%) unvaccinated individuals were enrolled. CD4⁺ T-cell responses of those individuals currently naturally infected were comparable to those who were 6 months from receiving their last dose of the vaccine; both responses were significantly higher than among those who were unvaccinated. Unvaccinated participants who became vaccinated while in the study showed a significant increase in both types of spike-specific immune responses. Previously vaccinated individuals who received a third dose (booster) showed a similar response to the spike protein. However, this response decreases as soon as 3 months but does not dip below the established response following two doses. Response to variants of concern B.1.617.2 (Delta) and B.1.1.529 (Omicron) also increased, with the Omicron variant having a significantly lower response when compared to Delta and the wild type. We conclude that antibody and T-cell responses increase in oncology workers after serial vaccination but can wane over time