Reduced neutralization against Delta, Gamma, Mu, and Omicron BA.1 variants of SARS-CoV-2 from previous non-Omicron infection.

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein.

Neutralization of alpha, gamma, and D614G SARS-CoV-2 variants by CoronaVac vaccine-induced antibodies.

Vaccination generates a neutralizing immune response against SARS-CoV-2. The genomic surveillance is showing the emergence of variants with mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we report the neutralization potency against alpha, gamma, and D614G SARS-CoV-2 variants in 44 individuals that received two doses of CoronaVac vaccine, an inactivated SARS-CoV-2 vaccine. Plasma samples collected at 60 days after the second dose of CoronaVac were analyzed by the reduction of cytopathic effect in Vero E6 cells with the three infectious variants of SARS-CoV-2. Plasma showed lower neutralization with alpha (geometric mean titer [GMT] = 18.5) and gamma (GMT = 10.0) variants than with D614G (GMT = 75.1) variant. Efficient neutralization against the alpha and gamma variants was not detected in 31.8% and 59.1% of plasma, respectively. These findings suggest the alpha and gamma variants could escape from neutralization by antibodies elicited by vaccination. Robust genomic and biological surveillance of viral variants could help to develop effective strategies for the control of SARS-CoV-2.

Genetic variability of human papillomavirus type 66 L1 gene among women presenting for cervical cancer screening in Chile.

The high-risk human papillomaviruses (HR-HPVs) are involved in the development of cervical cancer. Nevertheless, there are differences in the oncogenic potential among them. HPV-16 and HPV-18 are associated with approximately 70% of cancer worldwide, and both types are the most extensively studied HR-HPV. Great variations in the prevalence of HR-HPV have been described in different countries. The impact of these variations on the epidemiology of lesions and cervical cancer is currently unknown. A high prevalence of HPV-66 has been detected in Chile. Here, we have analyzed the genetic variability of the L1 gene from HPV-66-infected Chilean women. Higher order interactions between identified mutations were analyzed by co-variation and cluster analyses. Antigenic-index alterations following L1 mutations and B-cell epitopes were predicted by BcePred algorithm. HPV-66 L1 sequences clustered phylogenetically into two main clades. The genetic variability in the HPV-66 L1 gene involved thirty nucleotide changes. Four of these were for the first time identified in this study. Some of these variants are embedded in the B-cell epitope regions. Amino acid homology in the immunodominant epitopes of HPV-66 L1 protein (DE, FG and H1 loops) was 42.9-59.1% and 28.6-68.9% compared with HPV-16 and HPV-18, respectively. The results of this research suggest that the neutralizing epitopes of HPV-66 are antigenically different compared to HPV-16 and HPV-18. Our findings show the need to perform new structural and immunological studies on HPV-66 L1 protein to evaluate the cross-protection conferred by current HPV vaccines.

Detection and genotyping of HPV in urine samples from Chilean women attending primary health care centers.

Cervical cancer is the second most common malignant neoplasm in women worldwide representing approximately 10% of all types of cancers. Triage of women through cervical cytology has been an important strategy for the surveillance and control of new cases of cervical cancer. However, in many regions around the world cervical cytology has a low coverage compared to developed countries. The molecular detection of HPV is the most effective method to increase the screening sensitivity of women at risk of developing cervical cancer. There are very few studies about the efficacy of urine testing for detection of HPV in women followed up in primary health care centers. Consequently, the efficacy of using urine HPV screening in these populations has not been addressed yet. Here, we compared the detection of HPV in simultaneous urine and cervical samples of women followed up in primary health care centers. Urine and cervical samples were analyzed in 543 women attending at primary health care centers. HPV was detected by real time PCR, and HPV typing performed by PCR-RLB. A general HPV concordance of 86.2% (κ = 0.72) was determined between urine and cervical samples. The concordance for HPV-16 and 18 was almost perfect (κ = 0.82) and strong (κ = 0.77), respectively. The sensitivity and specificity for all HPV genotypes in urine using cervical samples as reference were 82.1 and 93.7%, respectively. The results showed that urine is a good alternative as clinical sample for HPV screening in women attending primary health care centers. Therefore, urine should be used as an alternative sample for increasing triage coverage either in refractory women participating in Pap surveillance programs or when cervical samples are not available.

Prevalence of human papillomavirus infection among women presenting for cervical cancer screening in Chile, 2014-2015.

Cervical cancer is the fourth most common malignancy in women worldwide. In Chile, cervical cancer is the second leading cause of death among women of reproductive age, causing more than 600 deaths annually. This study was carried out to determine the burden and confirm the predominant human papillomavirus (HPV) genotypes among women presenting for cervical cancer screening in public health services in Chile. Women aged 18-64 years residing in the north and central areas covered by six primary care centers of Santiago, Chile, were invited to participate from March 2014 to August 2015. Cervical swabs were examined both HPV genotyping by PCR and Reverse Line Blot, and cervical cytology by Pap testing. A total of 1738 women were included in this study: 11.1 % were HPV positive, 9.7 % were high-risk types positive, 3.2 % were low-risk types positive, 1.4 % were Pap positive and 0.9 % were positive by both tests. The four most predominant genotypes were 16, 66, 51 and 59, with prevalence of 2.8, 1.4, 1.2 and 1.2 %, respectively. Multiple HPV infections were detected among 3.8 % participants. Age-specific prevalence of HPV showed a peak in HPV infection at younger ages (≤30 years), declining to a plateau in middle age. Among women with normal cytology, the 9.4 % were HPV positive, while 58.3 % of women with abnormal cytology were HPV positive. These findings show new epidemiological data confirming HPV 16 and 66 as the most predominant genotypes in Chile. These data are important for design successful strategies for prevention of cervical cancer in Chile.