Potent Anti-Delta Effect By a Booster Third-Dose of UB-612, a Precision-Designed SARS-CoV-2 Multitope Protein-Peptide Vaccine (preprint)

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

Exposures to different SARS-CoV-2 spike variants elicit neutralizing antibody responses with differential specificity towards established and emerging strains (preprint)

The wide spectrum of SARS-CoV-2 variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of the immune response to different spike protein versions. Here, we compare the neutralization of variants of concern, including B.1.617.2 (Delta) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing one or more spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization. These findings contribute to understanding the relationship between exposures and antibody responses and may inform booster vaccination strategies.

High parental vaccine motivation at a neighborhood-based vaccine and testing site serving a predominantly Latinx community (preprint)

Purpose. To understand vaccine attitudes of Latinx parents highly impacted by COVID-19. Methods. In April 2021, we surveyed parents about their attitudes for COVID-19 vaccination of their children at a community-based outdoor testing/vaccination site serving predominantly low-income, Latinx persons in San Francisco. Results. Among 1,033 parents (75% Latinx), 92% would 'definitely' or 'probably' vaccinate their children. Vaccine hesitancy was higher for younger children; concerns included side effects and impacts on fertility. Doctors and community organizations were noted as trusted sources of information, including among vaccine-hesitant parents. Conclusion. Latinx parents accessing neighborhood-based COVID-19 testing/vaccination services are highly motivated to vaccinate their children for COVID-19.

A multi-component, community-based strategy to facilitate COVID-19 vaccine uptake among Latinx populations: from theory to practice (preprint)

Background COVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage. Methods and Findings Our community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategy's design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients at least 16 years old were used in the evaluation. There were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew 3 or more). Among clients who received both vaccine doses (n=729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to 3 or more) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence. Conclusions A multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.

Estimation of secondary household attack rates for emergent SARS-CoV-2 variants detected by genomic surveillance at a community-based testing site in San Francisco (preprint)

BackgroundSequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities. MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 2, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants. ResultsA total of 12,124 tests were performed yielding 1,099 positives. From these, 811 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.9% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to "West Coast" variants were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.357 vs 0.294, RR=1.29; 95% CI:1.01-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.1%). ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants; however, additional laboratory and epidemiological studies are required to better understand differences between these variants. SummaryWe observed a growing prevalence and elevated attack rate for "West Coast" SARS-CoV-2 variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.

A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model (preprint)

In this report, we describe the initial development and proof-of-concept studies for UB-612, the first multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen responsible for the Coronavirus Disease of 2019 (COVID-19). UB-612 consists of eight components rationally designed for induction of high neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist, and aluminum phosphate adjuvant. Through immunogenicity studies in guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provided excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses of the vaccine. Our candidate vaccine was then advanced into challenge studies, in which it reduced viral load and prevented development of disease in a mouse challenge model and in nonhuman primates (NHP, immunogenicity part is completed, challenge is ongoing). A GLP-compliant toxicity study has shown a favorable safety profile for the vaccine. With the Phase 1 trial ongoing in Taiwan and additional trials planned worldwide, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 transmission and COVID-19 disease.

Performance characteristics of a rapid SARS-CoV-2 antigen detection assay at a public plaza testing site in San Francisco (preprint)

We evaluated the performance of the Abbott BinaxNOWTM Covid-19 rapid antigen test to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured clinical SARS-CoV-2 yielded a human observable threshold between 1.6x104-4.3x104 viral RNA copies (cycle threshold (Ct) of 30.3-28.8 in this assay). Among 878 subjects tested, 3% (26/878) were positive by RT-PCR, of which 15/26 had a Ct<30, indicating high viral load. 40% (6/15) of Ct<30 were asymptomatic. Using this Ct<30 threshold for Binax-CoV2 evaluation, the sensitivity of the Binax-CoV2 was 93.3% (14/15), 95% CI: 68.1-99.8%, and the specificity was 99.9% (862/863), 95% CI: 99.4-99.9%.

Evaluation of a novel community-based COVID-19 'Test-to-Care model' for low-income populations (preprint)

BackgroundAfter a COVID-19 diagnosis, vulnerable populations face considerable logistical and financial challenges to isolate and quarantine. We developed and evaluated a novel, community-based approach ( Test-to-Care Model) designed to address these barriers for socioeconomically vulnerable Latinx individuals with newly diagnosed COVID-19 and their households. MethodsThis three-week demonstration project was nested within an epidemiologic surveillance study in a primarily Latinx neighborhood in the Mission district of San Francisco, California. The Test-to-Care model was developed with input from community members and public health leaders. Key components included: (1) provision of COVID-19-related education and information about available community resources, (2) home deliveries of material goods to facilitate safe isolation and quarantine (groceries, personal protective equipment and cleaning supplies), and (3) longitudinal clinical and social support. Newly SARS-CoV-2 PCR-positive participants were eligible to participate. Components of the model were delivered by the Test-to-Care team which was comprised of healthcare providers and community health workers (CHWs) who provided longitudinal clinic- and community-based support for the duration of the isolation period to augment existing services from the Department of Public Health (DPH). We evaluated the Test-to-Care Model using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework and drew upon multiple data sources including: programmatic data, informal interviews with participants and providers/CHWs and structured surveys among providers/CHWs. ResultsOverall, 83 participants in the surveillance study were diagnosed with COVID-19, of whom 95% (79/83) were Latinx and 88% (65/74) had an annual household income

SARS-CoV-2 Community Transmission During Shelter-in-Place in San Francisco (preprint)

ABSTRACT Background: We characterized SARS-CoV-2 infections in a densely-populated, majority Latinx San Francisco community six-weeks into the city's shelter-in-place order. Methods: We offered SARS-CoV-2 reverse transcription-PCR and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (>=4 years) and workers in a San Francisco census tract (population: 5,174) at outdoor, community-mobilized events over four days. We estimated SARS-CoV-2 point prevalence (PCR-positive) and cumulative incidence (antibody or PCR-positive) in the census tract and evaluated risk factors for recent (PCR-positive/antibody-negative) versus prior infection (antibody-positive/PCR-negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. Results: We tested 3,953 persons: 40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black. Overall, 2.1% (83/3,871) tested PCR-positive: 95% were Latinx and 52% asymptomatic when tested. 1.7% of residents and 6.0% of workers (non-census tract residents) were PCR-positive. Among 2,598 census tract residents, estimated point prevalence of PCR-positives was 2.3% (95%CI: 1.2-3.8%): 3.9% (95%CI: 2.0-6.4%) among Latinx vs. 0.2% (95%CI: 0.0-0.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95%CI: 4.0-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter-in-place and maintain income, frontline service work, unemployment, and household income