Targeted vaccination and the speed of SARS-CoV-2 adaptation

The limited supply of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises the question of targeted vaccination. Many countries have opted to vaccinate older and more sensitive hosts first to minimize the disease burden. However, what are the evolutionary consequences of targeted vaccination? We clarify the consequences of different vaccination strategies through the analysis of the speed of viral adaptation measured as the rate of change of the frequency of a vaccine-adapted variant. We show that such a variant is expected to spread faster if vaccination targets individuals who are likely to be involved in a higher number of contacts. We also discuss the pros and cons of dose-sparing strategies. Because delaying the second dose increases the proportion of the population vaccinated with a single dose, this strategy can both speed up the spread of the vaccine-adapted variant and reduce the cumulative number of deaths. Hence, strategies that are most effective at slowing viral adaptation may not always be epidemiologically optimal. A careful assessment of both the epidemiological and evolutionary consequences of alternative vaccination strategies is required to determine which individuals should be vaccinated first.

Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron variants

The omicron variant of concern (VOC) of SARS-CoV-2 was first reported in November 2021 in Botswana and South Africa. Omicron variant has evolved multiple mutations within the spike protein and the receptor binding domain (RBD), raising concerns of increased antibody evasion. Here, we isolated infectious omicron from a clinical specimen obtained in Canada. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron VOCs was assessed. Convalescent sera from unvaccinated individuals infected by the ancestral virus during the first wave of COVID-19 in Canada (July, 2020) demonstrated reduced neutralization against beta, delta and omicron VOCs. Convalescent sera from unvaccinated individuals infected by the delta variant (May-June, 2021) neutralized omicron to significantly lower levels compared to the delta variant. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of both delta and omicron variants relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Importantly, infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron. This data will inform current booster vaccination strategies and we highlight the need for additional studies to identify longevity of immunity against SARS-CoV-2 and optimal neutralizing antibody levels that are necessary to prevent infection and/or severe COVID-19.

Sequential immunization with SARS-CoV-2 RBD vaccine induces potent and broad neutralization against variants in mice

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.

Mathematical modelling of COVID-19 vaccination strategies in Kyrgyzstan

Objectives: In December 2020, an unprecedented vaccination programme to deal with the COVID-19 pandemic was initiated worldwide. However, the vaccine provision is currently insufficient for most countries to vaccinate their entire eligible population, so it is essential to develop the most efficient vaccination strategies. COVID-19 disease severity and mortality vary by age, therefore age-dependent vaccination strategies must be developed. Study design and Methods: Here, we use an age-dependent SIERS (susceptible, infected, exposed, recovered, susceptible), deterministic model, to compare four hypothetical age-dependent vaccination strategies and their potential impact on the COVID-19 epidemic in Kyrgyzstan. Results: Over the short-term (until March 2022), a vaccination rollout strategy focussed on high-risk groups (aged greater than 50 years) with some vaccination among high-incidence groups (aged 20 to 49 years) may decrease symptomatic cases and COVID-19-attributable deaths. However, there will be limited impact on the estimated overall number of COVID19 cases with the relatively low coverage of high incidence groups (15 to 25% based on current vaccine availability). Vaccination plus nonpharmaceutical interventions (NPIs), such as mask-wearing and social distancing will further decrease COVID-19 incidence and mortality and may have an indirect impact on all-cause mortality. Conclusions: Our results and other evidence suggest that vaccination is most effective in flattening the epidemic curve and reducing mortality if supported by NPIs. In the short term, focussing on high-risk groups may reduce the burden on the health system and result in fewer deaths. However, the herd effect from delaying another peak may only be achieved by greater vaccination coverage in high incidence groups.

Seven-Month Analysis of Five SARS-CoV-2 Antibody Assay Results after ChAdOx1 nCoV-19 Vaccination: Significant Decrease in SARS-CoV-2 Antibody Titer

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0–0.9% at T0, 66.2–92.5% at T1, 98.2–100.0% at T2, and 66.0–100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Streptococcal superantigens and the return of scarlet fever

Streptococcus pyogenes (group A Streptococcus) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet fever. Scarlet fever is a toxin-mediated disease characterized by the formation of an erythematous, sandpaper-like rash that typically occurs in children aged 5 to 15. This infectious disease is caused by toxins called superantigens, a family of highly potent immunomodulators. Although scarlet fever had largely declined in both prevalence and severity since the late 19th century, outbreaks have now reemerged in multiple geographical regions over the past decade. Here, we review recent findings that address the role of superantigens in promoting a fitness advantage for S. pyogenes within human populations and discuss how superantigens may be suitable targets for vaccination strategies.

mRNA Booster Vaccines Elicit Strong Protection Against SARS-CoV-2 Omicron Variant in Cancer Patients

Following its emergence in late November of 2020, the SARS-CoV-2 Omicron (B.1.1.529) variant has caused major global public health concerns. We recently demonstrated that in healthy adults the Omicron variant exhibits strong resistance to immunity induced by two doses of the mRNA vaccines, but a booster mRNA vaccine dose can provide strong protection against Omicron. However, it is currently unknown how well these mRNA vaccine boosters protect immunocompromised groups, including cancer patients, from the Omicron variant. Here we show that (1) neutralizing antibody (nAb) titers against the Delta and Omicron variants in cancer patients after two-dose mRNA vaccines are 4.2-fold and 21.3-fold lower, respectively, compared to the ancestral D614G, and (2) nAb titers against the Delta and Omicron variants in boosted cancer patients are 3.6-fold and 5.1-fold lower, respectively, compared to D614G. Our findings highlight the effectiveness and need for booster vaccination strategies in immunocompromised groups including cancer patients to protect from the Omicron variant.