Pneumococcal Phenotype and Interaction with Nontypeable Haemophilus influenzae as Determinants of Otitis Media Progression

All-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To understand the basis for the declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeable Haemophilus influenzae (NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout. Data included samples from OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1,588) from unvaccinated asymptomatic children in the same population. We compared data representing pneumococcal serotype diversity across carriage and disease isolates with and without NTHi coisolation. We also measured associations between the pneumococcal phenotype and the rate of progression from colonization to OM in the presence and absence of NTHi. Whereas pneumococcal serotype diversity was lower in single-species OM than in single-species colonization, levels of serotype diversity did not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and those differences were attenuated in polymicrobial episodes. Vaccine serotype pneumococci had higher rates of progression than nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM progression rate, efficient capsular metabolic properties-traditionally thought to serve as an advantage in colonization-predicted an enhanced rate of progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs

Vaccine-Induced Antibody Responses against SARS-CoV-2 Variants-Of-Concern Six Months after the BNT162b2 COVID-19 mRNA Vaccination

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concern about increased transmissibility, infectivity, and immune evasion from a vaccine and infection-induced immune responses. Although COVID-19 mRNA vaccines have proven to be highly effective against severe COVID-19 disease, the decrease in vaccine efficacy against emerged Beta and Delta variants emphasizes the need for constant monitoring of new virus lineages and studies on the persistence of vaccine-induced neutralizing antibodies. To analyze the dynamics of COVID-19 mRNA vaccine-induced antibody responses, we followed 52 health care workers in Finland for 6 months after receiving two doses of BNT162b2 vaccine with a 3-week interval. We demonstrate that, although anti-S1 antibody levels decrease 2.3-fold compared to peak antibody levels, anti-SARS-CoV-2 antibodies persist for months after BNT162b2 vaccination. Variants D614G, Alpha, and Eta are neutralized by sera of 100% of vaccinees, whereas neutralization of Delta is 3.8-fold reduced and neutralization of Beta is 5.8-fold reduced compared to D614G. Despite this reduction, 85% of sera collected 6 months postvaccination neutralizes Delta variant. IMPORTANCE A decrease in vaccine efficacy against emerging SARS-CoV-2 variants has increased the importance of assessing the persistence of SARS-CoV-2 spike proteinspecific antibodies and neutralizing antibodies. Our data show that after 6 months post two doses of BNT162b2 vaccine, antibody levels decrease yet remain detectable and capable of neutralizing emerging variants. By monitoring the vaccine-induced antibody responses, vaccination strategies and administration of booster doses can be optimized.Peer reviewe

Low pre-vaccination SARS-CoV-2 seroprevalence in Finnish health care workers: a prospective cohort study

Background: Health care workers are at risk of acquiring SARS-CoV-2 infection. Our aim was to study the prevalence of SARS-CoV-2 nucleoprotein and spike protein specific antibodies in health care workers with occupational exposure to COVID-19 in Turku, Finland, from May to December 2020.Methods: Health care workers of Turku University Hospital units caring for COVID-19 patients or handling clinical SARS-CoV-2 samples were invited to participate in the study. The presence of SARS-CoV-2 nucleoprotein and spike protein specific IgG antibodies were analysed with in-house enzyme immunoassay.Results: At study enrolment, only one of the 222 (0.5%) study participants was seropositive for SARS-CoV-2 protein specific antibodies. Two additional study participants (2/222, 0.9%) seroconverted during the follow-up. All these participants were diagnosed with a RT-PCR-positive COVID-19 infection before turning seropositive.Conclusion: In our study population, the prevalence of SARS-CoV-2 seropositivity remained low. The absence of seropositive cases without previous RT-PCR confirmed infections demonstrate good access to diagnostics. In addition to high vaccine coverage, high standards of infection prevention practices and use of standard personal protective equipment seem sufficient in preventing occupational SARS-CoV-2 infection in a setting with low number of circulating virus. However, it remains unclear whether similar protective practices would also be effective against more transmissible SARS-CoV-2 variants.</p

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n=180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants. Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al. show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.Peer reviewe

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants

Long-Lasting T Cell Responses in BNT162b2 COVID-19 mRNA Vaccinees and COVID-19 Convalescent Patients

The emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it more difficult to prevent the virus from spreading despite available vaccines. Reports of breakthrough infections and decreased capacity of antibodies to neutralize variants raise the question whether current vaccines can still protect against COVID-19 disease. We studied the dynamics and persistence of T cell responses using activation induced marker (AIM) assay and Th1 type cytokine production in peripheral blood mononuclear cells obtained from BNT162b2 COVID-19 mRNA vaccinated health care workers and COVID-19 patients. We demonstrate that equally high T cell responses following vaccination and infection persist at least for 6 months against Alpha, Beta, Gamma, and Delta variants despite the decline in antibody levels.</p

Persistent T cell-mediated immune responses against Omicron variants after the third COVID-19 mRNA vaccine dose

IntroductionThe prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations.MethodsIn this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs.ResultsHere we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4+ and CD8+ T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4+ T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose.DiscussionWe show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4+ and CD8+ T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n=180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants. Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al. show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.</p

Pneumococcal Phenotype and Interaction with Nontypeable Haemophilus influenzae as Determinants of Otitis Media Progression

All-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To understand the basis for the declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeable Haemophilus influenzae (NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout. Data included samples from OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1,588) from unvaccinated asymptomatic children in the same population. We compared data representing pneumococcal serotype diversity across carriage and disease isolates with and without NTHi coisolation. We also measured associations between the pneumococcal phenotype and the rate of progression from colonization to OM in the presence and absence of NTHi. Whereas pneumococcal serotype diversity was lower in single-species OM than in single-species colonization, levels of serotype diversity did not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and those differences were attenuated in polymicrobial episodes. Vaccine serotype pneumococci had higher rates of progression than nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM progression rate, efficient capsular metabolic properties-traditionally thought to serve as an advantage in colonization-predicted an enhanced rate of progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs