Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

The emergence of SARS-CoV-2 variants may impact the effectiveness of vaccines, while heterologous vaccine strategy is considered to provide better protection. The immunogenicity of an mRNA-inactivated virus vaccine against the SARS-CoV-2 wild-type (WT) and variants was evaluated in the study. SARS-CoV-2 naïve adults (n = 123) were recruited and placed in the following groups: BNT162b2, CoronaVac or BNT162b2-CoronaVac (Combo) Group. Blood samples were collected to measure neutralization antibodies (NAb) by a live virus microneutralization assay (vMN) and surrogate NAb test. The day 56 vMN geometric mean titre (GMT) was 26.2 [95% confident interval (CI), [22.3–30.9] for Combo, 136.9 (95% CI, 104.2–179.7) for BNT162b2, and 14.7 (95% CI, 11.6–18.6) for CoronaVac groups. At 6 months post-first dose, the GMT declined to 8.0, 28.8 and 7.1 in the Combo, BNT162b2 and CoronaVac groups, respectively. Three groups showed reduced neutralizing activity against D614G, beta, theta and delta variants. At day 56 GMT (74.6) and month 6 GMT (22.7), the delta variant in the BNT162b2 group was higher than that in the Combo (day 56, 7.4; month 6, 5.5) and CoronaVac groups (day 56, 8.0; month 6, 5) (p < 0.0001). Furthermore, the mean surrogate NAb value on day 56 in the BNT162b2 group was 594.7 AU/mL and higher than 40.5 AU/mL in Combo and 38.8 AU/mL in CoronaVac groups (p < 0.0001). None of the participants developed severe adverse events, and all other adverse events were self-limiting. The Combo vaccination strategy was safe. The overall vaccine immunogenicity at day 56 and 6 months were comparable to the homologous CoronaVac group but inferior to the homologous BNT162b2 group, against both the WT and all variants. Furthermore, the antibody response of vaccines waned at 6 months and thereby, a third dose of the vaccine is needed for these vaccines.

Antibody Response of BNT162b2 and CoronaVac Platforms in Recovered Individuals Previously Infected by COVID-19 against SARS-CoV-2 Wild Type and Delta Variant

Vaccinating recovered patients previously infected by COVID-19 with mRNA vaccines to boost their immune response against wild-type viruses (WT), we aimed to investigate whether vaccine platform and time of vaccination affect immunogenicity against the SARS-CoV-2 WT and Delta variant (DV). Convalescent patients infected by COVID-19 were recruited and received one booster dose of the BNT162b2 (PC-B) or CoronaVac (PC-C) vaccines, while SARS-CoV-2 naïve subjects received two doses of the BNT162b2 (CN-B) or CoronaVac (CN-C) vaccines. The neutralizing antibody in sera against the WT and DV was determined with live virus neutralization assay (vMN). The vMN geometric mean titre (GMT) against WT in recovered individuals previously infected by COVID-19 reduced significantly from 60.0 (95% confidence interval (CI), 46.5–77.4) to 33.9 (95% CI, 26.3–43.7) at 6 months post recovery. In the PC-B group, the BNT162b2 vaccine enhanced antibody response against WT and DV, with 22.3-fold and 20.4-fold increases, respectively. The PC-C group also showed 1.8-fold and 2.2-fold increases for WT and DV, respectively, after receiving the CoronaVac vaccine. There was a 10.6-fold increase in GMT in the CN-B group and a 1.3-fold increase in the CN-C group against DV after full vaccination. In both the PC-B and PC-C groups, there was no difference between GMT against WT and DV after vaccination. Subjects in the CN-B and CN-C groups showed inferior GMT against DV compared with GMT against WT after vaccination. In this study, one booster shot effectively enhanced the pre-existing neutralizing activity against WT and DV in recovered subjects.

Prevalence of Neutralising Antibodies to HCoV-NL63 in Healthy Adults in Australia

The COVID-19 pandemic has highlighted the importance of understanding the immune response to seasonal human coronavirus (HCoV) infections such as HCoV-NL63, how existing neutralising antibodies to HCoV may modulate responses to SARS-CoV-2 infection, and the utility of seasonal HCoV as human challenge models. Therefore, in this study we quantified HCoV-NL63 neutralising antibody titres in a healthy adult population using plasma from 100 blood donors in Australia. A microneutralisation assay was performed with plasma diluted from 1:10 to 1:160 and tested with the HCoV-NL63 Amsterdam-1 strain. Neutralising antibodies were detected in 71% of the plasma samples, with a median geometric mean titre of 14. This titre was similar to those reported in convalescent sera taken from individuals 3–7 months following asymptomatic SARS-CoV-2 infection, and 2–3 years post-infection from symptomatic SARS-CoV-1 patients. HCoV-NL63 neutralising antibody titres decreased with increasing age (R2 = 0.042, p = 0.038), but did not differ by sex. Overall, this study demonstrates that neutralising antibody to HCoV-NL63 is detectable in approximately 71% of the healthy adult population of Australia. Similar titres did not impede the use of another seasonal human coronavirus (HCoV-229E) in a human challenge model, thus, HCoV-NL63 may be useful as a human challenge model for more pathogenic coronaviruses.

Mycoplasma pulmonisinfection of the murine oropharynx protects against subsequent vaginal colonization

SummaryIntranasal inoculation of 12 young adult mice (strain TO) withMycoplasma pulmonisprotected all of them against vaginal colonization when they were challenged intravaginally 60 days later with the same mycoplasmal strain. In contrast, all 15 mice without a respiratory infection became colonized vaginally (geometric mean titre [GMT] 4·6 × 106colour-changing units [c.c.u.]) when challenged in the same way. The GMT of serum antibody, measured by a micro-immunofluorescence technique, prior to challenge was 200 and 8 for the oropharyngeally infected and unexposed mice, respectively. The GMT of antibody in vaginal washings from the two groups was 6 and 3, respectively. All four nude BALB/c mice were susceptible to vaginal colonization (GMT 5·6 × 106c.c.u.) after oropharyngeal infection (GMT 5·1 × 104c.c.u.) resulting from intranasal inoculation, as were all six nude mice (vaginal GMT 1·4 × 107c.c.u.) that had not been inoculated intranasally. In contrast, all ten of their immunocompetent counterparts were resistant to vaginal colonization after oropharyngeal infection (GMT 1·3 × 103c.c.u.), whereas all nine such mice that had not been infected oropharyngeally were susceptible to vaginal colonization (GMT 7·6 × 106c.c.u.). These results show the important role that a respiratory infection has in protecting the vagina against colonization and that protection is dependent on a functioning T-lymphocyte system.

Hotting-up the complement-fixation test

SUMMARYA detailed investigation into the effect of modifying the incubation temperature of the complement-fixation (CF) test is described. For varicella-zoster virus cytomegalovirus and rubella virus, increasing the incubation temperature progressively increased the sensitivity of the CF test to reach a maximum at 15°C, at which temperature the geometric mean titre of seropositive samples was significantly greater than that found at 4°C. For these three viruses, each serum shown to contain IgG antibodies by ultrasensitive radioimmunoassay procedures was detected by CF following incubation at 15°C. No false-positive reactions occurred at 15°C, but it was our impression that anticomplementary activity was enhanced at this temperature. Significant increases in antibody titre at 15°C were also seen when measles virus, respiratory syncytial virus, adenovirus and Mycoplasma pneumoniae were employed as CF antigens. The results demonstrate that the CF test should be performed at 15°C if optimum sensitivity is to be achieved. The ability of the test to detect significant rises in antibody titre was not impaired at the higher incubation temperature.

A new surface-antigen-adsorbed influenza virus vaccine II. Studies in a volunteer group

SUMMARYA group of 23 volunteers were each inoculated with 600 CCA of a new form of influenza virus A/England/42/72 vaccine; this vaccine consisted of purified haemagglutinin and neuraminidase antigens adsorbed to alhydrogel. No significant reactions to the vaccine were reported. Twenty-two volunteers produced increased titres of serum HI antibody, and all showed increased titres of NI antibody after immunization. Thus, for volunteers with no pre-immunization serum HI antibody, the geometric mean titre of serum antibody increased from 1/5 to 1/196 after immunization. Ten volunteers developed local neutralizing antibody after immunization; this antibody response was detected most frequently in volunteers who showed the greater serum antibody response to immunization, and in nasal washings with the higher concentrations of protein and IgA. Ten weeks after immunization, the vaccinees and a group of matched controls were inoculated intranasally with attenuated A/England/42/72 virus. Evidence of infection with the challenge virus was found in 14 of the control subjects and in one of the vaccinees. The results indicate that the surface-antigen-adsorbed vaccine induced high titres of serum antibody, and gave significant protection against challenge infection.

Epidemiological studies of Epstein–Barr herpesvirus infection in Western Australia

SUMMARYIn a study on a Caucasian population in Western Australia the prevalence of antibodies to Epstein–Barr virus (EBV) was 41% in the 9- to 10-year age group, 80% in the 16 to 19-year age group and 92% in young adults. The age-specific annual seroconversion rates indicated two peaks of primary EBV infection in the population studied – one under 5 years of age and the other at adolescence. The geometric mean titre rose with age, from 23 at 5–6 years to 53 at 36–40 years.It was shown that in 73 families studied there was evidence of probable spread of EBV infection among siblings, particularly between those of the same sex.Serological study of patients with infectious mononucleosis indicated that 100% of those examined had antibody to EBV and the geometric mean titre was elevated to 210. Rising titres and seroconversion was demonstrated in these patients together with successful establishment of EBV-carrying cell lines from the peripheral blood in two-thirds of the cases.