Longitudinal analysis of nursing home residents' T cell responses after SARS-CoV-2 mRNA vaccinations shows influence of biological sex and SARS-CoV-2 infection history.

BACKGROUND: Vaccines and vaccine boosting have blunted excess morbidity and mortality from SARS-CoV-2 infection suffered by 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 mRNA vaccines to SARS-CoV-2 in a cohort of NHR and healthcare workers (HCW) over 2 years. We used IFN-γ ELIspot and flow cytometry to assess T cell response before, two weeks and 6 months after the initial series and each of two booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T cell effector function. RESULTS: We show that prior SARS-CoV-2 infection and female sex contribute to higher T cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations and suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T cell response to mRNA vaccination.

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). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

Malaria Parasitemia and Severe Health Complications in Children Under Five Years of Age in Nigeria: A Study Using the Demographic and Health Survey (DHS) Malaria Indicator Survey (MIS) 2021.

BACKGROUND: In Nigeria, 97% of the population is at risk of contracting malaria. It is transmitted by female Anopheles mosquitoes carrying the Plasmodium parasite and can be lethal. An estimated 55 million illnesses and 80,000 deaths per year result from it. Children under five are more likely to contract malaria. Efforts to control malaria in Nigeria include indoor residual spraying, insecticide-treated bed nets, and quick detection and treatment of confirmed cases with effective antimalarial medications. These attempts have been impeded by limited healthcare access, poor financing, and drug-resistant parasites. Thus, the study of the relationship between malaria complications and housing for children under five is essential. METHODS: The Demographic and Health Survey (DHS) Malaria Indicator Survey (MIS) 2021, a nationally representative data set from developing countries on population and health, was used for this study. A sample size of 13,727 was employed (n=13,727). Logistic regression analyses were conducted to test the association between the type of place of residence and malaria complications (outcome). RESULTS: Overall, 4.2% (n=570, weight HV005) of participants in the sample reported malaria complications. The results of the logistic regression revealed that children residing in urban settlements (aOR 0.37, 95% CI 0.37-0.37, p-value <0.001), children from the poorest class families (aOR 11.63, 95% CI 1.62-1.63, p-value 0.004), children from poorer class families (aOR 7.56, 95% CI 7.55-7.57, p-value <0.001), children from middle-class families (aOR 4.05, 95% CI 4.03-9.06, p-value <0.001), children from richer class families (aOR 1.22, 95% CI 2.21-2.23, p-value <0.001), children of mothers with primary education (aOR 0.42, 95% CI 2.32-4.112, p-value 0.001), children of mothers with secondary education (aOR 0.24, 95% CI 3.21-3.22, p-value <0.001), children of mothers with higher education (aOR 0.08, 95% CI 0.72-0.80, p-value <0.001), and children of the female gender (aOR 0.65, 95% CI 0.65-0.66, p-value <0.001) are all associated with severe malaria complications. CONCLUSIONS: In conclusion, the study examined malaria complications in Nigerian children under five by residency. The findings imply that rural children are more likely to have serious malaria complications than urban children. This emphasizes the necessity for targeted malaria therapies in rural areas with limited healthcare access.

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.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

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. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.

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.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.

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 (N = 143) and HCWs (N = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.1) strain spike proteins, and by bead-multiplex immunoglobulin G immunoassay to Wuhan spike protein and its receptor-binding domain (RBD). Cytomegalovirus serology and levels of inflammatory biomarkers were also measured. Results: Severe acute respiratory syndrome coronavirus 2-naive CMV seropositive (CMV+) HCWs had significantly reduced Wuhan-neutralizing Ab (P = .013), anti-spike (P = .017), and anti-RBD (P = .011) responses 2 weeks after primary vaccination series compared with responses among CMV seronegative (CMV-) HCWs, adjusting for age, sex, and race. Among NH residents without prior SARS-CoV-2 infection, Wuhan-neutralizing Ab titers were similar 2 weeks after primary series but were reduced 6 months later (P = .012) between CMV+ and CMV- subjects. Wuhan-neutralizing Ab titers from CMV+ NH residents who had prior SARS-CoV-2 infection consistently trended lower than titers from SARS-CoV-2 experienced CMV- donors. These impaired Ab responses in CMV+ versus CMV- individuals were not observed after booster vaccination or with prior SARS-CoV-2 infection. Conclusions: Latent CMV infection adversely affects vaccine-induced responsiveness to SARS-CoV-2 spike protein, a neoantigen not previously encountered, in both HCWs and NH residents. Multiple antigenic challenges may be required for optimal mRNA vaccine immunogenicity in CMV+ adults.

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. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.

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. Optimization of vaccine usage will still be important to maximize protection due to reduced initial immunity, development of variant strains, and fading of immunity over time. There are also lessons learned specific to older populations for future pandemics of novel pathogens.

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.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).

Topical Photodynamic Therapy Generates Bioactive Microvesicle Particles: Evidence for a Pathway Involved in Immunosuppressive Effects.

Although effective in treating actinic damage, topical photodynamic therapy (PDT) has been shown to be immunosuppressive through unknown mechanisms, which could potentially limit its effectiveness. Multiple types of environmental stressors, including PDT, can produce the immunosuppressive lipid mediator platelet-activating factor (PAF). Because PAF can produce subcellular microvesicle particles (MVPs), these studies tested whether PDT can generate PAF and MVP release and whether these are involved in PDT-induced immunosuppression. Previously, topical PDT using blue light and 5-aminolevulinic acid was found to be a potent stimulus for PAF production in mice and human skin explants and human patients, and we show that experimental PDT also generates high levels of MVP. PDT-generated MVPs were independent of the PAF receptor but were dependent on the MVP-generating enzyme acid sphingomyelinase. Patients undergoing topical PDT treatment to at least 10% of body surface area showed local and systemic immunosuppression as measured by inhibition of delayed-type hypersensitivity reactions. Finally, using a murine model of contact hypersensitivity, PDT immunosuppression was blocked by genetic and pharmacologic inhibition of acid sphingomyelinase and genetic inhibition of PAF receptor signaling. These studies describe a mechanism involving MVP through which PDT exerts immunomodulatory effects, providing a potential target to improve its effectiveness.

COVID-19 vaccine booster dose needed to achieve Omicron-specific neutralisation in nursing home residents.

BACKGROUND: Nursing home (NH) residents have borne a disproportionate share of SARS-CoV-2 morbidity and mortality. Vaccines have limited hospitalisation and death from earlier variants in this vulnerable population. With the rise of Omicron and future variants, it is vital to sustain and broaden vaccine-induced protection. We examined the effect of boosting with BNT162b2 mRNA vaccine on humoral immunity and Omicron-specific neutralising activity among NH residents and healthcare workers (HCWs). METHODS: We longitudinally enrolled 85 NH residents (median age 77) and 48 HCWs (median age 51), and sampled them after the initial vaccination series; and just before and 2 weeks after booster vaccination. Anti-spike, anti-receptor binding domain (RBD) and neutralisation titres to the original Wuhan strain and neutralisation to the Omicron strain were obtained. FINDINGS: Booster vaccination significantly increased vaccine-specific anti-spike, anti-RBD, and neutralisation levels above the pre-booster levels in NH residents and HCWs, both in those with and without prior SARS-CoV-2 infection. Omicron-specific neutralisation activity was low after the initial 2 dose series with only 28% of NH residents' and 28% HCWs' titres above the assay's lower limit of detection. Omicron neutralising activity following the booster lifted 86% of NH residents and 93% of HCWs to the detectable range. INTERPRETATION: With boosting, the vast majority of HCWs and NH residents developed detectable Omicron-specific neutralising activity. These data provide immunologic evidence that strongly supports booster vaccination to broaden neutralising activity and counter waning immunity in the hope it will better protect this vulnerable, high-risk population against the Omicron variant. FUNDING: NIH AI129709-03S1, U01 CA260539-01, CDC 200-2016-91773, and VA BX005507-01.

Significant Reduction in Vaccine-Induced Antibody Levels and Neutralization Activity Among Healthcare Workers and Nursing Home Residents 6 Months Following Coronavirus Disease 2019 BNT162b2 mRNA Vaccination.

Antibody decline occurred from 2 weeks to 6 months post-BNT162b2 mRNA vaccination in nursing home (NH) residents and healthcare workers. Antispike, receptor-binding domain, and neutralization levels dropped >81% irrespective of prior infection. Notably, 69% of infection-naive NH residents had neutralizing antibodies at or below the assay's limit of detection.

Significantly elevated antibody levels and neutralization titers in nursing home residents after SARS-CoV-2 BNT162b2 mRNA booster vaccination.

Nursing home (NH) residents have experienced significant morbidity and mortality to SARS-CoV-2 throughout the pandemic. Vaccines initially curbed NH resident morbidity and mortality, but antibody levels and protection have declined with time since vaccination, prompting introduction of booster vaccination. This study assesses humoral immune response to booster vaccination in 85 NH residents and 44 health care workers (HCW) that we have followed longitudinally since initial SARS-CoV-2 BNT162b2 mRNA vaccination. The findings reveal that booster vaccination significantly increased anti-spike, anti-receptor binding domain, and neutralization titers above the pre-booster levels in almost all NH residents and HCW to significantly higher levels than shortly after the completion of the initial vaccine series. These data support the CDC recommendation to offer vaccine boosters to HCWs and NH residents on an immunological basis. Notably, even the older, more frail and more multi-morbid NH residents have sizable antibody increases with boosting.

Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents?

BACKGROUND: The BNT162b2 SARS-CoV-2 mRNA vaccination has mitigated the burden of COVID-19 among residents of long-term care facilities considerably, despite being excluded from the vaccine trials. Data on reactogenicity (vaccine side effects) in this population are limited. AIMS: To assess reactogenicity among nursing home (NH) residents. To provide a plausible proxy for predicting vaccine response among this population. METHODS: We enrolled and sampled NH residents and community-dwelling healthcare workers who received the BNT162b2 mRNA vaccine, to assess local or systemic reactogenicity and antibody levels (immunogenicity). RESULTS: NH residents reported reactions at a much lower frequency and lesser severity than the community-dwelling healthcare workers. These reactions were mild and transient with all subjects experiencing more local than systemic reactions. Based on our reactogenicity and immunogenicity data, we developed a linear regression model predicting log-transformed anti-spike, anti-receptor-binding domain (RBD), and neutralizing titers, with a dichotomous variable indicating the presence or absence of reported reactions which revealed a statistically significant effect, with estimated shifts in log-transformed titers ranging from 0.32 to 0.37 (all p < 0.01) indicating greater immunogenicity in subjects with one or more reported reactions of varying severity. DISCUSSION: With a significantly lower incidence of post-vaccination reactions among NH residents as reported in this study, the BNT162b2 mRNA vaccine appears to be well-tolerated among this vulnerable population. If validated in larger populations, absence of reactogenicity could help guide clinicians in prioritizing vaccine boosters. CONCLUSIONS: Reactogenicity is significantly mild among nursing home residents and overall, subjects who reported post-vaccination reactions developed higher antibody titers.

Reduced BNT162b2 Messenger RNA Vaccine Response in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Naive Nursing Home Residents.

After BNT162b2 messenger RNA vaccination, antibody levels to spike, receptor-binding domain, and virus neutralization were examined in 149 nursing home residents and 110 healthcare worker controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive nursing home residents' median post-second vaccine dose antibody neutralization titers are one-quarter that of SARS-CoV-2-naive healthcare workers.

Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents.

The SARS-CoV-2 pandemic impact on nursing home (NH) residents prompted their prioritization for early vaccination. To fill the data gap for vaccine immunogenicity in NH residents, we examined antibody levels after BNT162b2 mRNA vaccine to spike, receptor binding domain (RBD) and for virus neutralization in 149 NH residents and 111 health care worker controls. SARS-CoV-2-naive NH residents mount antibody responses with nearly 4-fold lower median neutralization titers and half the anti-spike level compared to SARS-CoV-2-naive healthcare workers. By contrast, SARS-CoV-2-recovered vaccinated NH residents had neutralization, anti-spike and anti-RBD titers similar to SARS-CoV-2-recovered vaccinated healthcare workers. NH residents' blunted antibody responses have important implications regarding the quality and durability of protection afforded by neoantigen vaccines. We urgently need better longitudinal evidence on vaccine effectiveness specific to NH resident populations to inform best practices for NH infection control measures, outbreak prevention and potential indication for a vaccine boost.