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1. Milk From Women Diagnosed With COVID-19 Does Not Contain SARS-CoV-2 RNA but Has Persistent Levels of SARS-CoV-2-Specific IgA Antibodies

   https://doi.org/10.3389/fimmu.2021.801797  

   Pace, Ryan M.; Williams, Janet E.; Järvinen, Kirsi M.; Meehan, Courtney L.; Martin, Melanie A.; Ley, Sylvia H.; Barbosa-Leiker, Celestina; Andres, Aline; Yeruva, Laxmi; Belfort, Mandy B.; et al (December 2021, Frontiers in Immunology)

   Background Limited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective To investigate whether SARS-CoV-2 can be detected in milk and on the breast after maternal coronavirus disease 2019 (COVID-19) diagnosis; and characterize concentrations of milk immunoglobulin (Ig) A specific to the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) during the 2 months after onset of symptoms or positive diagnostic test. Methods Using a longitudinal study design, we collected milk and breast skin swabs one to seven times from 64 lactating women with COVID-19 over a 2-month period, beginning as early as the week of diagnosis. Milk and breast swabs were analyzed for SARS-CoV-2 RNA, and milk was tested for anti-RBD IgA. Results SARS-CoV-2 was not detected in any milk sample or on 71% of breast swabs. Twenty-seven out of 29 (93%) breast swabs collected after breast washing tested negative for SARS-CoV-2. Detection of SARS-CoV-2 on the breast was associated with maternal coughing and other household COVID-19. Most (75%; 95% CI, 70-79%; n=316) milk samples contained anti-RBD IgA, and concentrations increased ( P =.02) during the first two weeks following onset of COVID-19 symptoms or positive test. Milk-borne anti-RBD IgA persisted for at least two months in 77% of women. Conclusion Milk produced by women with COVID-19 does not contain SARS-CoV-2 and is likely a lasting source of passive immunity via anti-RBD IgA. These results support recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness. 

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2. The Durability of Immunity against Reinfection by SARS-CoV-2: A Comparative Evolutionary Study

   https://doi.org/10.1016/S2666-5247(21)00219-6  

   Townsend, J.P.; Hassler, H.B.; Wang, Z.; Miura, S.; Singh, J.; Kumar, S.; Ruddle, N.; Galvani, A.P.; Dornburg, A. (December 2021, The Lancet microbe)

   Background: Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among evolutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63. Methods: We conducted phylogenetic analyses of the S, M, and ORF1b genes to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. We performed ancestral and descendent states analyses to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses. Findings: We obtained antibody optical density data for six human-infecting coronaviruses, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5-95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5-95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset. Interpretation: The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission-including among individuals who were previously infected with SARS-CoV-2-coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality. Funding: US National Science Foundation. 

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3. Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease

   https://doi.org/10.1038/s41541-022-00481-1  

   Davenport, Bennett J.; Catala, Alexis; Weston, Stuart M.; Johnson, Robert M.; Ardanuy, Jeremy; Hammond, Holly L.; Dillen, Carly; Frieman, Matthew B.; Catalano, Carlos E.; Morrison, Thomas E. (May 2022, npj Vaccines)

   Abstract The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the United States within 1 year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a “designer nanoparticle” platform using phage-like particles (PLPs) derived from bacteriophage lambda for a multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor-binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBD_SARS-PLPs and RBD_MERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBD_SARS- or RBD_MERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose-response studies, immunization with as little as one microgram of RBD_SARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBD_SARS-PLPs, RBD_MERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines. 

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4. Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease

   https://doi.org/10.1101/2021.11.08.467648  

   Davenport, Bennett J; Catala, Alexis; Weston, Stuart M; Johnson, Robert M; Ardunay, Jeremy; Hammond, Holly L; Dillen, Carly; Frieman, Matthew B; Catalano, Carlos E; Morrison, Thomas E (November 2021, bioRxiv)

   ABSTRACT The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the U.S. within one year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a “designer nanoparticle” platform using phage-like particles (PLPs) derived from bacteriophage lambda for multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBD_SARS-PLPs, RBD_MERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBD_SARS- or RBD_MERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose response studies, immunization with as little as one microgram of RBD_SARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBD_SARS-PLPs, RBD_MERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines. 

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5. COVID-19 Immunity Monitoring Using a Multiplexed Paper-Based Assay and Machine Learning

   Eryilmaz, M; Goncharov, A; Han, G; Joung, H; Ghosh, R; Zhang, Y; Di_Carlo, D; Ozcan, A (June 2024, 24th Annual University of California Systemwide Bioengineering Symposium)

   Monitoring the level of COVID-19 immunity within populations is crucial for understanding the disease trend and guiding public health policies, as SARS-CoV-2 remains a threat. Serological testing is essential in assessing immunity by detecting antibodies, IgG, and IgM, the immune system's response developed against infection or after vaccination. To rapidly and cost-effectively monitor COVID-19 immunity levels, we developed a paper-based multiplexed vertical flow immunoassay (xVFA) which detects the IgG and IgM levels in less than 20 mins, aiming to monitor the COVID-19 immunity levels of individuals longitudinally and categorize immune levels into three groups: protected, unprotected, and infected. 

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